Testicular torsion is a common urologic emergency and one of the causes of genital injury in males. Hence, early diagnosis and treatment are necessary to prevent testicular damage and infertility. It has been proved that topiramate (TPM) a medication used to treat epilepsy and prevent migraines has anti-inflammatory and anti-oxidative effects. Therefore, this study was designed to determine the influence of TPM on ischemia/reperfusion injury following testicular torsion/detorsion (T/D). Thirty-six male Wistar rats were divided into three groups (n = 12 for each group) including sham operated, T/D + vehicle, T/D + TPM(100 mg/kg, 30 min before detorsion). Testicular torsion was induced for 1 h by rotating right testis 720⁰ in the clockwise direction. After 5 h of reperfusion the testis was removed and histological changes and biochemical markers such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and levels of malondialdehyde (MDA) and reduced glutathione (GSH) were evaluated. MDA level significantly increased and GSH level significantly decreased after T/D compared to the sham group (p < 0.001). Moreover, after inducing testicular T/D, GPx, CAT and SOD activity were decreased, whereas administration of TPM significantly increased GSH level and GPx, CAT and SOD activities and decreased MDA level in testis tissue as compared to T/D group. After induction of T/D, histopathological evaluations also revealed severe testicular damages which were improved by TPM administration. Our results indicate that TPM had an ameliorating impact on ischemia/reperfusion injury in the rat model of testicular T/D. This protective effect was most likely induced by anti-oxidative properties of this drug.