Aim: this work was designed to investigate the effects of Thymoquinone and vitamin E pretreatment after 2 h of unilateral testicular torsion and their possible mechanism of action. Methods: the present study was performed on fifty male albino rats which were divided into five groups. Thymoquinone treated torsion/detorsion group, received pretreatment with Thymoquinone 100 mg/kg intraperitoneally 30 minutes before detorsion. Vitamin E treated torsion/detorsion group); received pretreatment with vit.E 100 mg/kg intraperitoneally 30 minutes before detorsion. Combined Thymoquinone and vit.E treated torsion/detorsion group received pretreatment in a dose of 100 mg/kg for each intraperitoneally 30 minutes before detorsion. Results: thymoquinone and vitamin E pretreatment caused significant decrease of malondialdehyde and nitric oxide levels and significant increase in reduced glutathione and glutathione peroxidase levels compared with untreated torsion/detorsion group. They improved testicular structures as they caused significant decrease in congestion, edema, and damage of seminiferous tubules in the ipsilateral and contralateral testis histologically when compared with torsion/detorsion group. Conclusion: the results suggest that early administration of Thymoquinone and vitamin E might have a protective effect for preventing testicular injury caused by testicular torsion probably through their antioxidant effects