Objective To investigate the molecular mechanism and protective effect of umbilical cord mesenchymal stem cells(umbilical cord mesenchymal stem cells,UC-MSCs)on necrotizing enterocolitis(necrotizing enterocolitis,NEC)in neonatal mice.Methods Neonatal C57BL/6 mice were selected to develop NEC mouse model by using hypertonic formula feeding,hypoxia and cold stimulation.30 mice were randomly divided into three groups(10 mice in each group):control group(breast feeding),necrotizing enterocolitis group(NEC+PBS)and mesenchymal stem cell therapy group(NEC+MSC).After treatment with UC-MSCs,the pathomorphological changes in intestine were evaluated by HE staining.The ex-pression of KI-67,a marker of epithelial cell proliferation,and myeloperoxidase(MPO),a marker of neutrophil infiltration,were detected by immunofluorescence staining;and the mRNA expression of leucine-rich repeat containing G protein-cou-pled receptor 5(Lgr5),interleukin 6(IL-6)and tumor necrosis factor(TNF-α)were detected by real-time fluorescence quantitative PCR.Results After UC-MSCs administration by intraperitoneal injection,the incidence of NEC decreased from 50%to 20%(P<0.05);the intestinal injury,macroscopic score and histopathological score were lower than the control group,(P=0.048 0 and 0.024 3,P<0.05).The number of KI-67 positive cells and Lgr5 gene expression increased significantly compared with the control group(P=0.012 9 and 0.030 4,P<0.05);MPO,IL-6 and TNF-α were significantly reduced compared with the control group(P=0.020 1,0.000 5 and 0.001 5,P<0.05).Conclusion UC-MSCs can reduce intesti-nal injury by promoting the proliferation of intestinal epithelial cells,modulating the activities of intestinal stem cells and re-ducing inflammation in NEC mice.