Numerous studies performed in recent years have shown protective effects of N-acetylcysteine (NAC) on cardiac and renal tissue damage following ischemia/reperfusion injury. We assessed the effectiveness of systemic administration of NAC, at a therapeutic dose, in a rat model of a 1-hour 720-degree testicular torsion/detorsion. Sprague-Dawley rats were divided into five groups, 14 animals in each: group 1 animals underwent sham operation as the control group; group 2 rats underwent torsion/detorsion and received saline injection, and the animals in groups 3, 4, and 5 received intraperitoneal injections of 150 mg/kg NAC 30 min before torsion, after torsion, and after detorsion, respectively. Markers of oxidative stress as well as germ cell apoptosis indices were assessed 4 and 24 h after detorsion, respectively. The apoptosis indices were significantly higher in group 2 as compared with the control group. Four hours after detorsion, the testicular level of lipid peroxidation was significantly increased, and antioxidant enzyme activities were significantly decreased in group 2 as compared with the controls. Administration of NAC either 30 min before or after torsion (groups 3 and 4) significantly improved the germ cell apoptosis indices and oxidant/antioxidant balance. Administration of NAC after detorsion had no significant effect on biochemical markers or germ cell apoptosis. Administration of NAC prior to torsion or detorsion, but not after detorsion, induces protective effects against ischemia/reperfusion injury in a rat model of testicular torsion. Copyright 2007 S. Karger AG, Basel.