Abstract: Objective To explore the therapeutic effect of umbilical mesenchymal stem cells transplantation(UMSCs)with over expression of chemokine receptor 4(CXCR4)in treatment of rats with acute liver failure induced by D-galactosamine and lipopolysaccharide(D-GalN/LPS). Methods The UMSCs of rats were separated by two-step method of collagenase and trypsin, and over expression of CXCR4 in UMSCs of rats were induced by serum of rats with acute liver failure. D-GalN/LPS was injected intraperitoneally to establish model of rats with acute liver failure. UMSCs(transplanted control group), UMSCs with high expression of CXCR4(transplanted treatment group)and equal amount of sterile phosphate buffer saline(PBS)solution(blank control group)were injected into the tail vein of rats at 24, 48, 96 and 144 hours after modeling. Blood samples were collected on the 3^rd and 7^th days after transplantation. Liver and lung tissue samples were collected on the 7^th day after transplantation. The 7-day survival rate, liver function, and pathological change of liver and lung were observed. Results The 7-day survival rate in the transplanted treatment group and the transplanted control group was 66.7% and 53.3% respectively, which was significantly higher than 20.0% - in the blank control group(P<0.05). The improvement of liver function and the liver inflammatory injury in the transplanted treatment group was significantly better than those in the transplanted control group and the blank control group(P<0.05), and no adverse reactions such as pulmonary embolism were observed. Conclusion UMSCs transplantation therapy has a significant effect in treatment of rats with acute liver failure induced by D-GalN/LPS, and UMSCs with high expression of CXCR4 has better effect.