Erectile dysfunction (ED) is a common problem in diabetic men, which affects the quality of life. Zosima absinthifolia (Vent.) Link (syn. Zosima orientalis Hoffm.) is the only member of Zosima genus growing in Turkey. Its fruits and aerial parts have been used in folk medicine as a sedative and digestive problems. This study aimed to investigate the possible beneficial effect of intracavernosal injection of umbelliferone isolated from Z. absinthifolia Link roots on ED of streptozotocin-induced diabetic rats. Adult Sprague-Dawley (n=20) rats were divided into control and streptozotocin-induced diabetic groups. In vivo erectile responses were also repeated after intracavernosal injection of umbelliferone (1 mu M). Umbelliferone-induced relaxant responses in the presence of inhibitors of nitric oxide synthase (NOS) and cyclic guanosine monophosphate (cGMP) were assessed in corpus cavernosum (CC) strips from control rats. The relaxant responses of CC strips from both groups were evaluated in the presence or absence of umbelliferone (100M). In vivo erectile responses in diabetic rats were significantly lower than in controls, which were partially prevented by umbelliferone. Umbelliferone resulted in a relaxation of CC in a concentration-dependent manner. NOS and cGMP inhibitors antagonized the umbelliferone-induced relaxations in CC. Acetylcholine, sodium nitroprusside, a phosphodiesterase type 5 inhibitor, sildenafil and electrical field stimulation-induced relaxation responses in diabetic CC strips were potentialized after pre-incubation with umbelliferone. In conclusion, intracavernosal administration of umbelliferone may prevent ED in diabetic rats by recovering of NO/cGMP pathway. These results may be supported by further studies using combinations of umbelliferone and phosphodiesterase type 5 inhibitors for the treatment of diabetic ED.