Disturbance in lipid metabolism can be both a cause and a consequence of the development of diabetes mellitus (DM). One of the most informative indicator of lipid metabolism is the ratio of atherogenic and antiatherogenic fractions of lipoproteins and their protein components. The review summarizes literature data and own results indicating the important role of high-density lipoprotein (HDL) and their main protein component, apolipoprotein A-I (apoA-I), in the pathogenesis of type 2 DM. On the one hand, HDL are involved in the regulation of insulin secretion by b-cells and insulin-independent absorption of glucose. On the other hand, insulin resistance and hyperglycemia lead to a decrease in HDL levels and cause modification of their protein component. In addition, HDL, possessing anti-inflammatory and mitogenic properties, provide anti-diabetic protection through systemic mechanisms. Thus, maintaining a high concentration of HDL and apoA-I in blood plasma and preventing their modification are important issues in the context of prevention and treatment of diabetes.