To investigate the correlation between estrogen related-receptor (ERR-y) and ATP-dependent K+ channel Kcnjl in renal ischemia-reperfusion injury and its possible role in regulating ischemic preconditioning. Methods The expression of ERR-y in kidney tissues was detected by immunohistochemistry. The expressions of ERR-y and Kcnjl in human renal tubular epithelial cells (HK-2) under hypoxia (1 % 02) were detected by RT-PCR. The ERR-y-deficient heterozygous mice model and the ERR-y-deficient completely mice model were established. The pretreatedischemia-reperfusion model were constructed in wild-type mice, EIRR-y-deficient heterozygous mice and ERR-y-deficient completely mice, respectively. Renal injury was observed under a light microscope with PAS staining. ERR-y and Kcnjl were tested by immunohistochemistry and RT-PCR. Results ERR-y in mice kidney tissue was mainly expressed in renal tubules, and the expressions of ERR-/and Kcnjl were decreased 59% and 29. 5% respectively after hypoxia in the renal tubular cells (HK-2). In the animal model, the expressions of ERR-y and Kcnjl were decreased 31.9% and 11% in early ischemic mice kidney tubular cells of wild type. The expressions of ERR-y and Kcnjl in renal tubular cells were decreased 33. 2% and 19. 1% after ischemia and reperfusion. When ERR-y were overexpressed in renal tubular cells, ERR-y was increased by 89% , and the expression of Kcnjl was increased by 72. 5% . The expression of Kcnjl was decreased by 75. 7% in ERR-y-deficient completely mice. However, Kcnjl expression in renal tissue of ERR-7-deficient mice was stable, but ischemic preconditioning failed to interfere with renal isehemia-reperfusion injury. Conclusion ERR/-Kcnjl is closely related to ischemic preconditioning and protects renal isehemia-reperfusion injury, and may be one of the regulatory factors. To explore the protective effect of the regulating pathway on ischemia reperfusion injury couldprovide a theoretical basis for the development of drug pretreatment.