〔Abstract〕 Objective To explore the effect of Icariin on pathological injury and oxidative stress in renal ischemia-reperfusion rats. Methods The rat model of renal ischemia-reperfusion was established and the rats were randomly divided into 5 groups: Control group, RIRI group, RIRI+icariin 25 mg/kg group, RIRI+icariin 50 mg/kg group and RIRI+icariin 100 mg/kg group for follow-up experiments. The kit was used to detect the levels of proteinuria, serum creatinine and urea nitrogen. HE staining was used to detect the degree of pathological damage. The contents of iNOS and IL-10 in peripheral blood and kidney tissues were detected by ELISA. The content of SOD and GSH was detected by the kit. Western blot was used to detect the expression levels of Caspase-3, Caspase-9, Bax, Bcl-2, Nrf2, p-Nrf2 and HO-1. Results The results showed that, compared with the Control group, the levels of proteinuria, serum creatinine and urea nitrogen in the RIRI group significantly increased(P<0.05), presenting significant renal ischemia-reperfusion injury, the cleaved Caspase-3/Caspase-3, cleaved Caspase-9/Caspase-9, and Bax/Bcl-2 ratios significantly increased(P<0.05), and the levels of inducible nitric oxide synthase(iNOS) and interleukin-10(IL-10) in the peripheral blood and renal tissues significantly increased(P<0.05). The contents of superoxide dismutase(SOD)and glutathione(GSH) significantly reduced(P<0.05), and the p-Nrf2/Nrf2 ratio and HO-1 protein level significantly reduced(P<0.05). Compared with the RIRI group, the levels of proteinuria, serum creatinine and urea nitrogen in the RIRI+icariin 50 and 100 mg/kg groups significantly reduced(P<0.05), and the degree of pathological damage was significantly improved. The ratios of cleaved Caspase-3/Caspase-3, cleaved Caspase-9/Caspase-9 and Bax/Bcl-2 significantly reduced(P<0.05), the iNOS content significantly reduced(P<0.05), and the IL-10 content significantly increased(P<0.05). The contents of SOD and GSH significantly increased(P<0.05). The p-Nrf2/Nrf2 ratio and HO-1 protein level significantly increased(P<0.05). Conclusion Icariin alleviates renal ischemia reperfusion injury and oxidative stress in rats by mediating Nrf2/HO-1 signaling pathway.