Numerous studies have demonstrated that diabetes associated hyperglycemia creates favourable conditions for overproduction of reactive oxygen species and the development of oxidative stress. Indeed, there is an increase of oxidative stress even at early stages of diabetes in children and adolescents. The results of recent studies suggest that excessive release of superoxide and hydrogen superoxide are responsible for intracellular activation of several intracellular pathways and alter the expression of genes in vascular cells that contribute to the pathogenesis of late diabetic complications. It has been demonstrated in experimental and clinical studies that high blood glucose concentration itself and related reactive oxygen species overproduction may alter endothelial cells structure and function and accelerate the initiation and progression of atherosclerosis. Because of its long history of proven efficacy and safety, gliclazide, a second generation sulfonylurea, is still widely used in monotherapy or in combination with other hypoglycemic agents. Beyond effective glycemic control, gliclazide appears to have extra-pancreatic effects, apparently independent of blood glucose lowering properties,. It has been demonstrated that gliclazide reduces proinflamatory markers, endothelial dysfunction, and platelets activity. These beneficial effects are likely mediated through the antioxidant properties of the drug. It seems that these unique features of gliclazide account for its capacity to inhibit the progression of atherosclerosis. Whether these properties translates into the ability to prevent the high incidence of cardiovascular morbidity and mortality in diabetic patients remains to be investigated.