Hyperglycemia is a common defining feature in the development of endothelial dysfunction which plays a key role in the pathogenesis of both type 1 and type 2 diabetes. Caveolin-1 is the main structural component of caveolae which might be involved in the pathophysiology of macrovascular complications of diabetes. In this study we aimed to observe the effect of caveolin-1 on functional responses of aorta and corpus cavernosum in the streptozotocin and fructose-induced diabetes groups. Type 1 diabetes was induced by intraperitoneal administration of streptozotocin (60 mg/kg),. Type 2 diabetes by adding fructose in the rat's drinking water (10% (w/v)) for 8 weeks. For insulin treatment; rats were treated with insulin (6 U/kg) for 8 weeks. In Type I and Type II diabetic groups the contractile responses of corpus cavernosum strips to phenylephrine (EC50:1.82 x 10(-5) M;1.47 x 10(-5) M, respectively)and relaxation responses to acetylcholine (EC50:7.5 x 10(-5) M;4.48 x 10(-5) M, respectively)were significantly impaired. Contractile responses of aortic-strips to phenylephrine in diabetic groups were markedly decreased (EC50:3.7. 10(-7) M;2.61. 10(-7) M respectively) and dose-dependent relaxation responses to acetylcholine were also attenuated (EC50:3.23 . 10(-6)M; 2.0. 10(-6)M respectively). Treatment with insulin improved the functional responses in the aorta and corpus cavernosum. Protein expression of caveolin-1 was increased in the aorta and corpus cavernosum of the diabetic groups, but this increase seen in the streptozotocin group was more significant than the fructose group. Our findings indicate that an attenuation of the functional responses in both diabetes groups were probably associated with an enhanced expression of caveolin-1, and therefore a decrease in the eNOS activity with a concomitant decrease in NO synthesis. (C) 2010 Elsevier B.V. All rights reserved.