Diabetes mellitus (DM) is a major health issue, with over 536.6 million patients aged 20–79 in 2021, projected to rise to 783.2 million by 2045. DM causes various complications, including diabetic cardiomyopathy (DCM), diabetic nephropathy (DN), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN), which significantly reduce quality of life. Inflammation plays a critical role in the pathogenesis of these complications, with immune cells, cytokines, and chemokines contributing to tissue damage and disease progression. Macrophages, for example, can shift from M2 to M1 phenotypes, promoting inflammation and fibrosis. Cytokines like TNF-α, IL-6, and TGF-β1 are involved in various pathological processes, including myocardial fibrosis, glomerular injury, and retinal damage. Inflammation also disrupts glucose homeostasis, leading to insulin resistance (IR), which exacerbates complications. Inflammation is linked to the development of atherosclerosis, kidney dysfunction, retinal damage, and neuropathy. Therapeutic strategies targeting inflammation, such as modulating macrophage polarization, inhibiting inflammatory cytokines, or using anti-inflammatory drugs, are being explored to treat DM complications. Understanding the molecular mechanisms of inflammation in DM complications is crucial for developing effective interventions. This review summarizes the current understanding of inflammation's role in DM complications and highlights potential therapeutic approaches.Diabetes mellitus (DM) is a major health issue, with over 536.6 million patients aged 20–79 in 2021, projected to rise to 783.2 million by 2045. DM causes various complications, including diabetic cardiomyopathy (DCM), diabetic nephropathy (DN), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN), which significantly reduce quality of life. Inflammation plays a critical role in the pathogenesis of these complications, with immune cells, cytokines, and chemokines contributing to tissue damage and disease progression. Macrophages, for example, can shift from M2 to M1 phenotypes, promoting inflammation and fibrosis. Cytokines like TNF-α, IL-6, and TGF-β1 are involved in various pathological processes, including myocardial fibrosis, glomerular injury, and retinal damage. Inflammation also disrupts glucose homeostasis, leading to insulin resistance (IR), which exacerbates complications. Inflammation is linked to the development of atherosclerosis, kidney dysfunction, retinal damage, and neuropathy. Therapeutic strategies targeting inflammation, such as modulating macrophage polarization, inhibiting inflammatory cytokines, or using anti-inflammatory drugs, are being explored to treat DM complications. Understanding the molecular mechanisms of inflammation in DM complications is crucial for developing effective interventions. This review summarizes the current understanding of inflammation's role in DM complications and highlights potential therapeutic approaches.