Background: Renal ischemia/reperfusion injury (RIRI) is the most common cause of acute kidney injury. We tested the protective role of endothelin-1 receptor blocker; bosentan (BOS) in animal model of RIRI in two different genders. Methods: Male and female Wistar rats were assigned as sham operated (sham), control group (ischemia), and case group (ischemia + BOS) treated with BOS (50 mg/kg) 2 h before bilateral kidney ischemia induced by clamping renal vessels for 45 min followed by 24 h of renal reperfusion. Results: The RIRI significantly increased the serum levels of blood urea nitrogen and creatinine in both genders (P < 0.05). These values were significantly decreased by BOS in both genders. In male rats, the serum levels of malondialdehyde in the ischemia + BOS group were decreased significantly when compared with ischemia group (P < 0.05). Conclusions: BOS can be used in both genders to attenuate kidney ischemia injury possibly due to its effect in the renal vascular system.