Patients with diabetes mellitus (DM) have a high prevalence of coronary artery disease (CAD), as diabetes is implicated in the formation of atherosclerotic plaque. Endothelial dysfunction is one of the precursor key steps in the development of atherosclerosis in diabetic subjects. Decreased nitric oxide (NO) production, increased oxidative stress and impaired function of endothelial progenitor cells are the main mechanisms involved in the accelerated atherosclerotic process observed in type 2 DM patients. Therapeutic approaches including classic agents such as statins, angiotensinconverting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), antioxidants and novel agents such as tetrahydrobiopterin (BH4), asymmetric dimethylarginine (ADMA) and homocysteine (tHcy), have been implicated in order to ameliorate endothelial function of diabetic patients.