Non-enzymatic modification of proteins by reducing sugars, a process that is also known as Maillard reaction, leads to the formation of advanced glycation end products (AGEs) in vivo. There is a growing body of evidence that formation and accumulation of AGEs progress during normal aging, and at an extremely accelerated rate under diabetes, thus being involved in the pathogenesis of diabetic vascular complications. Further, recently, engagement of their receptor, RAGE with AGEs is shown to activate its down-stream signaling and evoke oxidative stress and inflammation in diabetes. Since oxidative stress generation and inflammation are closely associated with insulin resistance as well, it is conceivable that the AGEs-RAGE system could play a role in the pathogenesis of insulin resistance and subsequently the development of diabetes. In this paper, we review the role of the AGEs-RAGE system in insulin resistance, especially focusing on its effects on the insulin-signaling pathways in skeletal muscles and adipocytes.