Endothelial dysfunction plays a key role in the pathogenesis of microangiopathy and macroangiopathy in type 2 diabetes mellitus. The endothelial dysfunction is induced by some cell metabolism disorders which are implicated in the pathogenesis of micro- and macroangiopathies through the principal mediation of oxidative stress. The discussion focuses preferentially on the recently found molecular mechanisms of free radical generation and on the endothelial disorders resulting from some free-radical-induced abnormalities in the intracellular signal pathways. We specify the molecular targets in the vascular complication therapy of diabetes on the basis of evidence of association between oxidative stress, metabolic abnormalities and endothelial dysfunction.