Macrophages play a critical role in metabolic disease, particularly in obesity and insulin resistance. This review discusses how macrophage activation and recruitment contribute to metabolic homeostasis, focusing on the pathogenic and protective functions of classically activated (M1) and alternatively activated (M2) macrophages in obesity and metabolic disease. Obesity leads to chronic, low-grade inflammation, primarily mediated by innate and adaptive immune cells, which is a key link between obesity and its metabolic consequences. In obese adipose tissue, macrophages exhibit a pro-inflammatory, classical (M1) phenotype, while in lean tissue, they have an alternatively activated (M2) phenotype. M2 macrophages secrete IL-10, which enhances insulin sensitivity, whereas M1 macrophages secrete pro-inflammatory cytokines that induce insulin resistance via IKKβ and JNK pathways. Obesity-induced insulin resistance is characterized by impaired glucose disposal and increased triglyceride lipolysis in adipose and skeletal muscle tissues, leading to hyperinsulinemia, hyperglycemia, and hyperlipidemia. The liver shows partial insulin resistance. Insulin resistance in these tissues leads to increased insulin secretion by β-cells, which can eventually result in β-cell exhaustion and type 2 diabetes. Macrophage-mediated inflammation contributes to insulin resistance through various mechanisms, including the activation of inflammatory pathways, secretion of pro-inflammatory cytokines, and the recruitment of inflammatory monocytes and macrophages into adipose tissue. The inflammasome, a multiprotein complex, is also involved in obesity-induced inflammation and insulin resistance. T cell activation in obese adipose tissue contributes to chronic inflammation and insulin resistance. Pathogenic Th1 cells and CD8+ T cells play a role in this process, and their depletion can improve insulin sensitivity. Alternatively activated macrophages, which are associated with Th2-type immunity, play a protective role in obesity-induced metabolic disease. PPARγ and PPARδ are involved in the regulation of alternative macrophage activation, which helps to reduce inflammation and insulin resistance. KLF4 and IL-4 signaling also contribute to alternative macrophage activation and the amelioration of obesity-induced insulin resistance. The source of IL-4 in adipose tissue is primarily eosinophils, which are involved in the alternative activation of macrophages and the protection against obesity and insulin resistance. Infection and immunity are closely linked to insulin resistance. In bacterial infections, insulin resistance is an adaptive mechanism that allows the body to divert nutrients to support immune function. In contrast, helminth infections are associated with Th2-type immunity, which enhances insulin action and nutrient storage. In conclusion, macrophages mediate a dynamic crosstalk between immunity and metabolism, playing a key role in the pathogenesis of metabolic disease. Understanding the mechanisms of macrophage activation and their interactions with metabolic tissues is crucial for developing therapeuticMacrophages play a critical role in metabolic disease, particularly in obesity and insulin resistance. This review discusses how macrophage activation and recruitment contribute to metabolic homeostasis, focusing on the pathogenic and protective functions of classically activated (M1) and alternatively activated (M2) macrophages in obesity and metabolic disease. Obesity leads to chronic, low-grade inflammation, primarily mediated by innate and adaptive immune cells, which is a key link between obesity and its metabolic consequences. In obese adipose tissue, macrophages exhibit a pro-inflammatory, classical (M1) phenotype, while in lean tissue, they have an alternatively activated (M2) phenotype. M2 macrophages secrete IL-10, which enhances insulin sensitivity, whereas M1 macrophages secrete pro-inflammatory cytokines that induce insulin resistance via IKKβ and JNK pathways. Obesity-induced insulin resistance is characterized by impaired glucose disposal and increased triglyceride lipolysis in adipose and skeletal muscle tissues, leading to hyperinsulinemia, hyperglycemia, and hyperlipidemia. The liver shows partial insulin resistance. Insulin resistance in these tissues leads to increased insulin secretion by β-cells, which can eventually result in β-cell exhaustion and type 2 diabetes. Macrophage-mediated inflammation contributes to insulin resistance through various mechanisms, including the activation of inflammatory pathways, secretion of pro-inflammatory cytokines, and the recruitment of inflammatory monocytes and macrophages into adipose tissue. The inflammasome, a multiprotein complex, is also involved in obesity-induced inflammation and insulin resistance. T cell activation in obese adipose tissue contributes to chronic inflammation and insulin resistance. Pathogenic Th1 cells and CD8+ T cells play a role in this process, and their depletion can improve insulin sensitivity. Alternatively activated macrophages, which are associated with Th2-type immunity, play a protective role in obesity-induced metabolic disease. PPARγ and PPARδ are involved in the regulation of alternative macrophage activation, which helps to reduce inflammation and insulin resistance. KLF4 and IL-4 signaling also contribute to alternative macrophage activation and the amelioration of obesity-induced insulin resistance. The source of IL-4 in adipose tissue is primarily eosinophils, which are involved in the alternative activation of macrophages and the protection against obesity and insulin resistance. Infection and immunity are closely linked to insulin resistance. In bacterial infections, insulin resistance is an adaptive mechanism that allows the body to divert nutrients to support immune function. In contrast, helminth infections are associated with Th2-type immunity, which enhances insulin action and nutrient storage. In conclusion, macrophages mediate a dynamic crosstalk between immunity and metabolism, playing a key role in the pathogenesis of metabolic disease. Understanding the mechanisms of macrophage activation and their interactions with metabolic tissues is crucial for developing therapeutic