The aim of this study was to evaluate and compare the effects of 5-lipoxygenase enzyme (5-LO) inhibitor zileuton and cysteinyl leukotriene receptor (CysLT1R) antagonist montelukast in testicular torsion/detorsion (T/D) injury model in rats. Rats were anaesthetised with 75 mg kg−1 ketamine hydrochloride and 8 mg kg−1 xylazine intraperitoneal before the operation. Torsion was created by rotating the right testis 720° clockwise and maintained by fixing the testis. The rats were treated with CysLT1R antagonist montelukast (10 mg kg−1; i.p.), 5-LO inhibitor zileuton (3 mg kg−1; i.p.), and vehicle, at 30 min prior detorsion. After 1 h of torsion, the testis was counter-rotated to the natural position and replaced into the scrotum. Malondialdehyde (MDA) level was measured in testicular tissue after 3 h of reperfusion. Histological examination was performed after 24 h of reperfusion. T/D caused a significant increase in MDA level and histopathological injury in testes. Montelukast and zileuton treatments prevented the T/D-induced augmentation in MDA levels. Only zileuton treatment significantly reduced the T/D-induced histopathological injury. In this study, we demonstrated for the first time that zileuton had protective effects on testicular T/D injury. We have also found that zileuton is more effective than montelukast on histopathological injury.