Aims: Induced pluripotent stem cells (iPSs) are believed to have great therapeutic potential. Treatment for acute kidney injury is challenging. Therefore, we aimed to demonstrate if iPSs attenuate acute kidney injury and the possible mechnisms. Methods: In vivo experiments: Male C57BL/6 mice were anesthetized with an intraperitoneal injection of 4% sodium pentobarbital (Nembutal). Kidneys were exposed and subjected to right nephrectomy, followed by left renal ischemia for 50min, then resuscitated with Ringer’s lactate. After operation, the mice were injected iPSs with or without 100uM NAC pre-treated. The kidney tissue and serum were collected 24 h, 48h after resuscitation. Creatinine, pathology score, cytokine expression, iPSs quantification and identification in injury kidney were detected. In vitro EC- iPSs experiments: mice glomerular endothelial cells isolated from C57BL/6 were pre-treated with MCP-1 (10 U/ml) 4h, and then added iPSs with or without NAC(100 uM) treated. Following that the adhesion and transendothelial migration of IPS were detected. Results: In vivo study showed iPSs decreased the scores from 2.5±0.2 at 24h and 3.9±0.1 at 48h in mice receiving PBS to 1.1±0.1 and 0.25±0.1, respectively. The scores of mice receiving NAC-pretreated iPSs were in between. The serum creatinine levels to 248.14±13.66 umol/L at 24h and 280.94±9.89 umol/L at 48h. Intravenous injection of iPSs decreased serum creatinine levels to 99.54±4.65 umol/L at 24h and 93.9±4.58 umol/L at 48h . The serum creatinine level had no significant difference between mice receiving PBS and NAC-pretreated iPSs.Administration abolished the increases in the expressions of IL-6, GRO, and GM-CSF in the kidney. NAC-pretreated iPSs had the same effect as untreated iPSs. The positive cells were found in the kidney that received iPS or NAC-pretreated iPSs, but not in the mice that received PBS by FISH staining. In vitro study showed the rate of adhesion of iPSs to MCP-1-activated GEC was significantly higher than to untreated GEC. NAC-pretreatment decreased the transendothelial migration of iPSs by 47.2% , adhesion to activated GEC by 57.1%, and adhesion to untreated GEC by 14.4%. Innovation and conclusion: The novel findings of the present study included isogenic iPSs decreased renal ischemia/reperfusion injury. iPSs selectively homed to injured kidneys and became an integrated part of glomeruli and renal tubules in a ROS-dependent manner. Our results also showed that iPSs can be regulated by modulating either iPSs themselves or the endothelial cells of target tissue.