Macrophages play a crucial role in the human body's innate immunity and are involved in various inflammatory diseases. They can polarize into two main phenotypes: pro-inflammatory M1-like macrophages and anti-inflammatory M2-type macrophages. The balance between these two phenotypes is critical for maintaining homeostasis. Imbalance can lead to various inflammatory conditions, including autoimmune diseases, allergic diseases, atherosclerosis, obesity, and type 2 diabetes. In autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), and autoimmune hepatitis (AIH), an imbalance in M1/M2 macrophage ratios is linked to disease progression. M1-like macrophages produce pro-inflammatory cytokines, while M2-like macrophages have anti-inflammatory properties. Therapeutic strategies targeting macrophage polarization, such as using CTLA4-Ig and FA-AgNPS, have shown promise in treating these conditions. In allergic diseases like allergic rhinitis, allergic dermatitis, and allergic asthma, M1-like macrophages are often associated with severe symptoms. Research has identified compounds that can modulate macrophage polarization to alleviate allergic responses, such as Naringenin and Diosmetin. Atherosclerosis, a chronic arterial disease, is characterized by inflammation and the formation of atherosclerotic plaques. M1-like macrophages contribute to plaque progression, while M2-like macrophages play a role in inhibiting plaque formation. Therapeutic approaches targeting macrophage polarization, including traditional Chinese medicine and statins, have shown potential in treating atherosclerosis. Type 2 diabetes (T2DM) and obesity are closely linked to macrophage polarization. T2DM is associated with high-sugar diets and comorbidities like periodontitis. Obesity increases the risk of T2DM and insulin resistance. High-intensity interval training (HIIT) and activation of the EP4 receptor have been shown to shift macrophage polarization to an anti-inflammatory state, improving metabolic disorders. Overall, understanding and manipulating macrophage polarization offers new therapeutic opportunities for managing inflammatory diseases. Further research is needed to optimize these strategies for clinical applications.Macrophages play a crucial role in the human body's innate immunity and are involved in various inflammatory diseases. They can polarize into two main phenotypes: pro-inflammatory M1-like macrophages and anti-inflammatory M2-type macrophages. The balance between these two phenotypes is critical for maintaining homeostasis. Imbalance can lead to various inflammatory conditions, including autoimmune diseases, allergic diseases, atherosclerosis, obesity, and type 2 diabetes. In autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), and autoimmune hepatitis (AIH), an imbalance in M1/M2 macrophage ratios is linked to disease progression. M1-like macrophages produce pro-inflammatory cytokines, while M2-like macrophages have anti-inflammatory properties. Therapeutic strategies targeting macrophage polarization, such as using CTLA4-Ig and FA-AgNPS, have shown promise in treating these conditions. In allergic diseases like allergic rhinitis, allergic dermatitis, and allergic asthma, M1-like macrophages are often associated with severe symptoms. Research has identified compounds that can modulate macrophage polarization to alleviate allergic responses, such as Naringenin and Diosmetin. Atherosclerosis, a chronic arterial disease, is characterized by inflammation and the formation of atherosclerotic plaques. M1-like macrophages contribute to plaque progression, while M2-like macrophages play a role in inhibiting plaque formation. Therapeutic approaches targeting macrophage polarization, including traditional Chinese medicine and statins, have shown potential in treating atherosclerosis. Type 2 diabetes (T2DM) and obesity are closely linked to macrophage polarization. T2DM is associated with high-sugar diets and comorbidities like periodontitis. Obesity increases the risk of T2DM and insulin resistance. High-intensity interval training (HIIT) and activation of the EP4 receptor have been shown to shift macrophage polarization to an anti-inflammatory state, improving metabolic disorders. Overall, understanding and manipulating macrophage polarization offers new therapeutic opportunities for managing inflammatory diseases. Further research is needed to optimize these strategies for clinical applications.