To investigate the effect of EPO gene modified human amniotic mesenchymal stem cell transplantation on renal function and renal cell apoptosis in ischemic-reperfusion-induced acute kidney injury (AKI) rats. Human amniotic mesenchymal stem cells were cultured in vitro; retroviral virus PLXSN was used as the vector to mediate erythropoietin (EPO) gene transfection; it was divided into three groups: control group, negative transfection group, EPO transfection group. EPO protein in human amniotic mesenchymal stem cells was detected by Western blot after transfection; 68 SD rats were selected (male: female 1:1), weighing 220-260 g. Non-invasive artery clamp was used to clamp bilateral renal pedicle for 40 min; ischemia-reperfusion induced AKI model was established (after modeling there were a total of eight demyelination and death). The rats were divided into EPO-AM-MSCs (EPO-amniotic membrane-mesenchymal stem cells) group, AM-MSCs group and the control group, 20/group. On day 3, 28 after the transplantation left kidney specimens of 5 rats in three groups were stained by HE staining to observe renal tissue damage; TUNEL assay was used to detect renal cell apoptosis; on day 28 after transplantation fluorescence microscope was used to observe PKH-26 labeled AM-MSCs survival and distribution. In 1, 3, 14, 28 days after modeling serum creatinine (SCr) and blood urea nitrogen (BUN) were detected. At 3, 28 days after transplantation, HE staining examination showed that in EPO-AM-MSCs group tubular damage scores were 2.1 +/- 0.12, 1.2 +/- 0.10; in AM-MSCs group, tubular damage scores were 3.1 +/- 0.12, 2.1 +/- 0.11; in the control group tubular damage scores were 3.9 +/- 0.16, 2.8 +/- 0.13; the differences between two groups were statistically significant (P < 0.05). At 28 days after transplantation, PKH-26 positive cells: EPO-AM-MSCs group > AM-MSCs transplantation group > the control group; The difference between the groups was statistically significant (P < 0.05). At 3, 28 days after transplantation, TUNEL-positive apoptotic cells: the control group > AM-MSCs group > EPO-AM-MSCs group; The difference was statistically significant (P < 0.05) between groups. At 3, 14, 28 days after transplantation, serum levels of creatinine and blood urea nitrogen: EPO-AM-MSCs group < AM-MSCs group < control group (P < 0.05). EPO gene-modified human amniotic mesenchymal stem cell transplantation had a significant repair effect on rat acute kidney injury.