Background: Testicular torsion is a medical emergency that requires urgent surgical intervention. Aim: To study the effect of erythropoietin (EPO) on unilateral testicular ischemia/reperfusion (I/R) in rats.Methods: 32 adult male wistar rats were divided into 4 equal groups; sham-operated group, 2 hours torsion group, untreated torsion/detorsion (T/D) group and EPO-treated T/D group. In all groups testicular malondialdehyde (MDA), catalase activity, nitrite/ nitrate and tumor necrosis factor-alpha (TNF-α) were measured in testicular tissue. Free testosterone was measured in serum. Caspase-3 was examined by immunohistochemistry. Histopathological examination of testicular tissue was also done for all groups.Results: At the end of the experimental period, the 2 hours torsion and untreated T/D groups showed significant increases in testicular MDA, nitrite/ nitrate and TNF-α and significant reduction of testicular catalase activity and serum free testosterone. These biochemical results were significantly reversed in EPO-treated T/D group. These results were corroborated by immunohistochemistry of caspase-3 and histopathological results of testicular tissue in all groups. Conclusion: From these results, it is concluded that, EPO plays an important beneficial role in I/R injury of testis due to its antioxidant, antiinflammatory, antiapoptotic and angiogenic properties and can be used as a novel therapeutic approach in conjunction with surgical repair to decrease the rate of surgical resection of torted testis.