Erectile dysfunction occurs frequently in humans with diabetes mellitus; the molecular basis of this phenomenon is not known. We investigated the effects of diabetes on penile erection, nitric oxide synthase and growth factors expression in an animal model. Forty male rats were divided into two groups: the experimental group (n 30) received intraperitoneal injection of Streptozotocin (STZ) dissolved in citrate buffer to induce diabetes; ten age-matched control rats received injection of citrate buffer vehicle only. Before euthanization at eight weeks, erectile function was assessed by electrostimulation of the cavernous nerves. NADPH diaphorase staining was used to identify NOS and immunostaining technique was used to identify nNOS in the penile nerve ®bers. RT-PCR was used to identify mRNA expression of nNOS, eNOS, iNOS, ER-b b, ER-a, NGF, IGF-I, TGF-b1, and AR. Western blot was used to identify nNOS, IGF-I, NGF, and TFG-b protein expressions. In the diabetic group, there was: (1) a signi®cant decrease in NOS containing nerve ®bers in the dorsal and intracavernosal nerves; (2) a signi®cant lower maximal intracavernosal pressure. RT-PCR showed down-regulation of nNOS (large form), iNOS and ER-b mRNA expression, Immunoblot showed down-regulation of nNOS protein expression and nNOS immunostaining showed less positive staining in the dorsal and intracavernous nerves in the diabetic group. These molecular changes may provide the basis for further studies to explore the association between diabetes and impotence.