Chronic psychological stress cause erectile dysfunction (ED). Considering, recent evidence that tumor necrosis factor-a (TNF-alpha) levels are increased in serum of patients with ED, the present study investigated the effects of infliximab (a TNF-a blocker) on endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) :immunoreactivity of rat penile corpus cavernosum in unpredictable chronic mild stress (UCMS):. Male adult rats were randomly divided into three groups (n = 8 per group): Control, UCMS and UCMS+infliximab. Control and UCMS groups received physiological saline, UCMS+infliximab group received infliximab (5 mg kg(-1) per week; intraperitoneally) during 8 weeks of UCMS. UCMS and UCMS+infliximab groups were subjected to different types of stressors, which were randomly applied four to five times during this time period. After 8 weeks, penile eNOS'and,nNOS expressions were determined immunohistochemicaliy. In. UCMS group, nNOS and eNOS immunoreactivity was found to be-decreased in penile. corpuscavernosum compared with the control group. Whereas in infliximab treatment group eNOS and nNOS immunoreactivity increased compared with the UCMS group. These findings support that UCMS decreases penile constitutive NOS expression via TNF-alpha, which may contribute to the development of ED. Blockage of TNF-alpha actions may represent an alternative therapeutic approach for ED in chronic psychological stress.