Background: It is generally accepted that an excessive production of reactive oxygen species plays an important role in acute renal failure secondary to ischemia and reperfusion. tert-Butylhydroquinone (tBHQ) is a well-known antioxidant. In this study, we evaluated whether tBHQ pretreatment prevented renal damage induced by ischemia and reperfusion (I/R). Methods: Four groups of rats were studied: (a) controlsham (CT), (b) tBHQ-sham (tBHQ), (c) I/R and (d) tBHQ + I/R. Intraperitoneal (i.p.) injections of tBHQ (50 mg/ kg) were given to the tBHQ and tBHQ + I/R groups and 3% ethanol/isotonic saline solution to the CT and I/R groups. Animals were killed 24 hours after I/R. Results: tBHQ attenuated I/R-induced renal dysfunction, structural damage, oxidative/nitrosative stress, glutathione depletion and the decrease in several antioxidant enzymes. Conclusion: The renoprotective effect of tBHQ on I/R injury was associated with the attenuation in oxidative/nitrosative stress and the preservation of antioxidant enzymes.