Objective：To explore the protective effect of erythropoietin derived peptide on renal ischemia-reperfusion injury in mice and to investigate its influence on PI3K/Akt signal transduction pathway. Methods：The mice were divided into the sham operation group，the model group and the study group. The animal model of renal ischemia-reperfusion injury was repeated. Erythropoietin derived peptide was injected into the abdominal cavity of mice in the model group 6 hours before operation，and normal saline was injected into the abdominal cavity in the sham operation group and the model group. Serum creatinine（Scr） in different groups was detected by picric acid rate method，urine nitrogen（BUN） level was detected by enzymology rate method，renal pathological changes were examined through pathological section，renal cell apoptosis was analyzed by in situ end labeling，and expression levels of nase B，protein kinase B（Akt），phosphorylated protein kinase B（p-Akt），cysteine aspartate protease（caspase-3） were detected by Western blot. Results：Levels of SCR and BUN in the model group were significantly higher than those in the sham operation group，while in the study group were significantly lower than those in the model group（P<0.05）. The renal pathological damage in the study group was significantly weaker than that in the model group，only a small part of the renal tubular epithelial cells were swollen，rare renal tubular epithelial cells had necrosis and abscission and the renal tubular lumen was normal. The score of renal pathological in－jury was significantly higher than that in the sham operation group，and in the study group was significantly lower than that in the model group（P<0.05）. The apoptosis score of the renal tubular epithelial cells in the model group was significantly higher than that in the sham operation group，and in the study group was significantly lower than that in the model group（P<0.05）. The expression level of renal caspase-3 protein in the model group was significantly higher than that in the sham operation group（P<0.05） and the expression level of Akt and p-Akt protein in the operation group was significantly lower than that in the sham operation group（P<0.05）；the expression level of renal caspase-3 protein in the study group was significantly lower than that in the sham oper－ation group，and the expression level of Akt and p-Akt protein was significantly higher than that in the sham operation group（P<0.05）. Conclusion：Erythropoietin derived peptide has a significant improvement on renal ischemia-reperfusion，which may be achieved by regulating PI3K/Akt signal transduction pathway and regulating the expression of apoptotic protein.