Endothelium-dependent relaxation was examined in aortic ring preparations obtained from rats with streptozotocin-induced diabetes. The endothelium-dependent relaxation which was produced by acetylcholine and histamine in aortic rings precontracted with norepinephrine was significantly attenuated in aortic rings from diabetic rats when compared with the relaxation in rings from age-matched control animals. However, the relaxation induced by sodium nitroprusside (an endothelium-independent relaxant agent) in diabetic preparations was comparable to the control. These results show that diabetes leads to an impairment of the endothelium-dependent relaxation of aorta.