The aim of this study was to evaluate the relaxant effect of resveratrol (RVT), one of the most commonly employed dietary polyphenols, in rat corpus cavernosum, and to further investigate the contribution of possible underlying mechanisms. Strips of corpus cavernosum were used in organ baths for isometric tension studies. RVT (10-6-10-4 M) produced concentrationdependent relaxation responses in rat corpus cavernosum precontracted by phenylephrine. The relaxant responses to RVT partially, but significantly inhibited by removal of endothelium. Nitric oxide (NO) synthase (NOS) blocker N-nitro-L-arginine methyl ester (l-NAME, 10-4 M) or soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10-5 M) caused a significant inhibition on relaxation response to RVT, whereas cyclooxygenase inhibitor indomethacin (10-5 M) did not significantly alter relaxant responses of corpus cavernosum strips to RVT. Corpus cavernosum contractions induced by stepwise addition to Ca2+ to high KCI solution with no Ca2+ were significantly inhibited by RVT incubation. The treatment of corpus cavernosum tissues with non-specific potassium channel inhibitor tetraethylammonium (TEA, 10-2M) did also significantly affect the relaxant activity of RVT. Otherwise, the relaxation response of corpus cavernosum induced by the phosphodiesterase-5 inhibitor sildenafil increased significantly in the group pretreated with 10-5 M RVT. These results demonstrated that RVT has a potent relaxant effect on rat corpus cavernosum via endothelium-dependent and -independent mechanisms. Endothelium-dependent relaxation of corpus cavernosum to RVT is thought to be mediated primarily through NO/cGMP signaling pathway, and possibly an additional mechanism, endothelium-dependent hyperpolarization factor (EDHF). The residual endothelium-independent corpus cavernosum relaxation induced by RVT is uncertain but seems to depend on the interactions of RVT with Ca2+ entry mechanism from the extracellular space and also other undefined direct effects in this tissue.