〔Abstract〕 Objective To explore the protective effect and mechanism of human umbilical cord derived mesenchymal stem cells(hUC-MSCs) on neurons by transplanting hUC-MSCs and treating hypoxic ischemic encephalopathy(HIE) in neonatal rats induced by hypoxia and ischemia. Methods About 10 cm umbilical cord of normal full-term healthy newborns born was collected under sterile conditions, and hUC-MSCs were cultured by tissue block adherent method, and then infected with recombinant adenovirus carrying green fluorescent protein. 18 healthy 7-day-old SD rats were randomly divided into normal control( sham operation) group,model group and h UC-MSCs treatment group,6 in each group. After 24 h of modeling,hUC-MSCs were injected into the left ventricle of the treatment group. After 48 h of h UC-MSCs transplantation,h UC-MSCs were detected in the brain of HIE rats and TTC staining was used to observe the infarcted brain tissue. The mR NA levels of Beclin-2 and Caspase-3 in hippocampus were detected by RT-qPCR. Western blot was used to detect the expression of Beclin-2 and Caspase-3. Results 48 h after hUC-MSCs transplantation in HIE group,there was no infarct volume in normal control group,and the infarct volume ratio was( 41. 67 ± 4. 17) %; in hUC-MSCs treatment group,the infarct volume ratio was( 16. 65 ± 3. 43) %,which was significantly lower than that in hypoxic-ischemic brain injury group. 48 h after HIE modeling,the expression of endogenous beclin-2 mR NA and caspase-3 mR NA,beclin-2 protein and caspase-3 protein were significantly up-regulated. 48 h after hUC-MSCs transplantation,the expression of beclin-2 mR NA,caspase-3 mR NA,beclin-2 protein and caspase-3 protein decreased. Conclusion h UC-MSCs can effectively reduce the infarct volume of rats with hypoxic-ischemic injury,which has a protective effect on the injured rats; at the same time,hUC-MSCs can significantly reduce the apoptosis of rat brain cells,and significantly down regulate the levels of beclin-2 mR NA,caspase-3 mR NA,beclin-2 protein and caspase-3 protein in hippocampus of rats with hypoxic-ischemic brain injury.