Aims: The aim of this study was to examine the effects of leptin on aortic rings with and without endothelium isolated from streptozotocin (STZ)-diabetic and control rats and in the presence of an inhibitor of nitric oxide synthase. Methods: STZ (50 mg/kg, i.p.)-induced diabetic (n=12) and age-matched control (n=12) Sprague-Dawley male rats were anaesthetized with i.p. injections of 60 mg/kg ketamine and were sacrificed with decapitation. Thoracic aortic rings with and without endothelium were mounted in isolated tissue baths. Concentration-response curves to leptin (10-13 – 10-9 M) were constructed under basal tone and after precontracted with 10-6 M phenylephrine in the presence or absence of Nω-nitro-L-arginine methyl ester (L-NAME, 10-5 M). The study protocol was approved by The Animal Experimentation Ethics Committee of Selcuk University. Results: Leptin caused a concentration-dependent relaxation in the precontracted endothelium intact aortic rings from diabetic and control rats. Responses to leptin in diabetic aorta were significantly increased compared to those of control. The maximum response (Emax) of control aortic rings to leptin was 38.3 ± 4.6%, while that of diabetic rings was 56.5 ± 5.2% (P<0.05). EC50 values for leptin were similar for aortic rings from diabetic (7.5 ± 1.6 x 10-12) and control rats (5.5 ± 1.2 x 10-12, P> 0.05). L-NAME pretreatment caused complete inhibition in the relaxant responses to leptin of the control aortic rings while it induced a reduction in these responses of the diabetic rings (Emax:21.8 ± 4.3%, p<0.05; EC50: 7.0 ± 1.4 x10-12). Leptin-induced relaxations were abolished when the endothelium was denuded. Leptin had no effect on basal tone of endothelium intact and denuded aortic rings from control rats. In diabetic rings, leptin (10-13-10-9 M) elicited dose dependent contraction (Emax: 22.3 ± 4.2%, p<0.05, n=8). Removal of endothelium significantly increased contractile effect of leptin on basal tone in diabetic rings (Emax: 55.2 ± 5.7%, P<0.05). Conclusion: Reduced nitric oxide-dependent relaxant response to leptin may have been compensated by another endothelial mechanism(s) in diabetic rat aorta. On the other hand, leptin causes contractile effect on the basal tone in aorta smooth muscle isolated from STZ-induced diabetic rats.