Diabetes mellitus is known to produce alterations in vascular reactivity. In the present study we have examined the effects of endothelium-dependent and endothelium-independent relaxing substances on thoracic aorta from insulin-dependent (Type-1) and noninsulin-dependent (Type-2) diabetic rats and their appropriate controls. Endothelium-dependent relaxations produced by acetylcholine and histamine in aortic rings precontracted with noradrenaline were significantly increased in insulin-dependent diabetic vessels. In contrast, the relaxations elicited by those agents were significantly attenuated in noninsulin-dependent diabetic aorta preparations. On the other hand, the relaxations induced by sodium nitroprusside (an endothelium-independent relaxant agent) in both types of diabetic preparations were comparable to those in control vessels. The results indicate that insulin-dependent and noninsulin-dependent diabetes lead to specific alterations of the endothelium-dependent relaxation of rat aorta.