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Cardiovascular disease is the leading cause of disease / mortality worldwide. It is generally accepted that increased production of reactive oxygen species (ROS) has an important role in cardiovascular pathology, contributing to endothelial dysfunction and to the aggravation of atherosclerosis. Among all cardiovascular risk factors, diabetes mellitus is one of the most important. The worldwide prevalence of diabetes has increased rapidly even in developing countries, doubling the combined risk of cardiovascular events in patients with hypertension. In diabetes, increased reactive oxygen species (ROS) production leads to endothelial dysfunction, recognized by the presence of impaired vascular relaxation, increased vascular smooth muscle cells growth and hypertrophy, all together contributing to atherosclerotic plaque formation. On this basis, the vascular endothelium has emerged as a therapeutic target, with the aim to improve systemic metabolic state by improving vascular function. In this review we have focused on the most important sources of reactive oxygen species generated by vascular endothelium in diabetic patients (NADPH Oxidases, eNOS uncoupling, Xanthine oxidase). The importance of oxidative stress in mediating the vascular complications of diabetes is supported by studies showing that antioxidant therapy correct the vascular function in humans or in experimental models of diabetes. Therefore, understanding the physiological mechanisms involved in vascular disorders resulting from hyperglycemia is essential for the proper use of available therapeutic resources.