Oxidative stress and inflammation response have been found to be associated with renal ischemia reperfusion (I/R) injury through an undefined mechanism. The aim of our study is to explore the influence of Wnt/beta-catenin signaling pathway on oxidative stress and inflammation response during renal I/R injury. The results of our study demonstrated that oxidative stress was induced whereas antioxidative factors were suppressed by renal I/R injury. Besides, the transcriptions and activities of pro-inflammation factors were also upregulated by renal I/R injury. Interestingly, inhibition of Wnt/beta-catenin signaling pathway significantly attenuated I/R-mediated oxidative stress and inflammation response. Therefore, our results report a novel pathway responsible for renal I/R injury. Inhibition of Wnt/beta-catenin signaling pathway would be considered as an effective approach to regulate oxidative stress and inflammation response in reperfused kidney.