Magnesium deficiency has recently been proposed as a novel factor implicated in the pathogenesis of diabetes complications. Previous studies have shown that magnesium decreases basal tone in normal isolated aortic rings and reduces phenylephrine-induced contraction. The mechanism of this magnesium action is not very well known. The present study was designed to determine the role of endothelium and nitric oxide in magnesium sulfate-induced vasorelaxation in diabetic rat vessels. Diabetes was induced by a single tail injection of streptozotocin. Eight weeks later, superior mesenteric arteries of control and diabetic animals were isolated and perfused according to the McGregor method. Prepared vascular beds were constricted with phenylephrine to induce 70-75% of maximal constriction. Magnesium sulfate at concentrations of 0.001 M to 0.1 M was added into the medium and perfusion pressure was then recorded. Mesenteric bed baseline perfusion pressure in intact and denuded endothelium of diabetic groups was higher than controls. In all groups, relaxant response to magnesium in mesenteric bed was attenuated after endothelium removal, but a relaxatory effect appears at high concentration. In the presence of N (omega)-nitro-L-arginine methyl ester (L-NAME), magnesium-induced relaxation was significantly suppressed in intact mesenteric bed of control animals but in diabetics, the relaxant response was slightly inhibited. From the results of this study, it can be concluded that magnesium-induced endothelium dependent and endothelium independent vasorelaxation are mediated by nitric oxide in control rats while in diabetic animals other mechanisms may be involved.