Background: Sildenafil citrate (Viagra) is widely used for the treatment of erectile dysfunction with various etiologies. Aim of the work: This study was designed to investigate the histological changes as a result of chronic use of sildenafil citrate on smooth muscles of rat corpus cavernosum and blood vessels. Material and Methods: paraffin sections from rat corpus cavernosum and blood vessels were obtained from sixty rats divided in to two groups, control and experamintal group. Last group was sub classified in to group I, II and III receiving 1mg, 2mg and 3mg of sildenafil citrate for three months, stained with Hematoxylin and eosin, Masson’s trichrome and Weigert then examined by light microscopy. Quantitative morphometric studies followed by statistical analysis of the data were done. Specimens were prepared and examined by electron microscopy. Results: Light microscopic examination showed that at corpus cavernosum congestion of blood sinusoids in group I and II which became partially collapsed due to gradual increased collagen fibers. This finding was more manifested by increasing dose of sildenafil cirtate in group III. Gradual decrease in smooth muscles was also recorded .These histological changes were detected by histological, histochemical stains and image analyzer as well as TEM. Increase collagen fiber may be due to increase protein synthesis activity of smooth muscles which may cause fibrosis in penile tissue. Considering the histological results of blood vessels comparing sections of group I, II and III with those of control group, revealed increased thickness of tunica intima and media due to increased collagen fibers content both in tunica media and adventitia as proved by image analyzer. Controversy there was decrease in smooth muscles content in the tunica media and No changes were detected in elastic fibers of blood vessels. Conclusion: chronic use of sildenafil citrate causes decrease in smooth muscles and increase collagen fibers in corpus cavernosum of penis and wall of blood vessels.