Abstract: Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia due to multiple etiological factors. In diabetics, lipid accumulation may cause lipid peroxidation and cell membrane lipid oxidation, leading to cellular injuries and triggering dysfunctions. Lipid accumulation may also lead to kidney injury in diabetics, such as glomerulosclerosis, tubular injury and loss of podocytes. As a water-soluble low molecular glycoprotein, apolipoprotein C3 (APOC3) is an important factor in the regulation of human lipid metabolism. It is closely involved in the development of diabetes mellitus and related complications through insulin resistance, lipid metabolism disorders, inflammation and oxidative stress. This review summarized the role and mechanism of APOC3 in diabetes and diabetic kidney disease.