Abstract: Objective：To explore the effect of transplantation of human umbilical mesenchymal stem cells (HUMSCs) carrying angiotensin converting enzyme 2 (ACE2) gene in treatment of acute lung injury (ALI) induced by bleomycin in rats. Methods：HUMSCs were isolated from the umbilical cord of normal mature infants delivered by caesarean section, and flow cytometry was used to identify the cell surface antigen. The virus granules Lenti-ACE2 were prepared by three-plasmid co-transfection method in 293T cells, and then were transfected into HUMSCs. The rats were randomly divided into normal control group, BLM group, ACE2 group, HUMSCs group, and HUMSCs-ACE2 group (n=24). The rats were dripped by BLM (5 mg/kg) in endotracheal to establish ALI rat model except normal control group. The broncho-alveolar lavage fluid (BALF) and lung tissue were collected to detect the related indicators before and 3, 7, 14 days after BLM dripping. The number of neutrophils and total protein content in alveolar lavage were determined by counting method and BCA method, respectively. The histopathological morphology of lung was observed by H-E staining, the activity of myeloperoxidase (MPO), the levels of INF-γ and IL-4 mRNA, the level of TNF-α and the expression of ACE2 protein in lung tissue were respectively determined by chemical method, RT-PCR, ELISA method and Western blotting. Results：The neutrophil count and total protein content in BALF in HUMSCs group, ACE2 group and HUMSCs-ACE2 group showed a trend of decline compared with that in BLM group at 3, 7, 14 days time points, especially in HUMSCs-ACE2 group (P<0.05). Pathological grading of lung injury severity showed that the lung tissue injury was significantly improved in ACE2, HUMSCs, HUMSCs-ACE2 group rats compared with BLM group, especially in HUMSCs-ACE2 group (P<0.05) 3, 7, and 14 days after injury. Compared with BLM group at the same time points, the expression of ACE2 in HUMSCs-ACE2 group had the most obvious increment, reaching the peak at the 14th day (P<0.05). Compared with BLM group at the same time points, the MPO activity and INF-γ mRNA were decreased, the IL-4 mRNA was increased in HUMSCs, ACE2, and HUMSCs-ACE2 group, especially in HUMSCs-ACE2 group (all P<0.05). Immunofluorescence staining indicated that the exogenous HUMSCs carried ACE2/eGFP gene, and there were many GFP cells in the damaged lung tissue at the 14th day after intravenous transfusion of HUMSCs. Conclusions：Transplantation of HUMSCs carrying ACE2 gene can effectively reduce the neutrophil infiltration and total protein leakage, improve the vascular permeability, decrease the levels of proinflammatory factors, increase the levels of anti-inflammatory factors such as IL-4 and ACE2 in lung tissue in ALI rats, thus alleviates pathological injury of the lung.