〔Abstract〕 Objective To observe the interventional effects of human amniotic mesenchymal stem cells(hAMSCs) transfected with angiotensin converting enzyme 2(ACE2) gene on monocrotaline-induced pulmonary arterial hypertension(PAH) in rats. Methods (1) HAMSCs were transfected with lentivirus carrying ACE2 gene, and the expression of ACE2, insulin-like growth factor(IGF-1), granulocyte chemoattractant protein-2(GCP-2) gene, cell migration and tube formation ability was detected before and after transfection.(2) Male, healthy, 6-week-old SD rats were randomly divided into normal Control group(Control group), pulmonary hypertension group(PAH group), human amniotic mesenchymal stem cell treatment group(hAMSCs group) and ACE2-transfected human amniotic mesenchymal stem cell treatment group(ACE2-hAMSCs group). The mean pulmonary arterial pressure(mPAP) and right ventricular hypertrophy index(RVHI) were measured 2 weeks after the model was established. The lumen size of pulmonary arterioles and the thickness of vessel wall were observed by HE staining. The mRNA expression levels of GCP-2, ACE2, α-actin and angiotensin Ⅱ(Ang Ⅱ) in lung tissue were determined by QPCR. Results In vitrocell experiments showed that the cell migration ability and tube formation ability of ACE2-hamscs were higher than those of pure hAMSCs(P<0.05). Ace2-hamscs up-regulated the mRNA expressions of ACE2 and pro-angiogenic factors IGF-1 and GCP-2(P<0.01). After 2 weeks of intervention, the mPAP and cardiac RV/LV+S of the PAH group significantly increased compared with the normal control group(P<0.01), and the mPAP and cardiac RV/LV+S of the ACE2-hAMSCs group significantly decreased compared with the PAH and hAMSCs groups(P<0.01). Compared with PAH group, the mRNA expression level of ACE2 significantly increased in the lung tissue of ACE2-hamscs group. Conclusion ACE2-hAMSCs can significantly reduce the mean pulmonary arterial pressure of monocrotaline(MCT)-induced PAH rat model, and significantly improve pulmonary vascular and right ventricular remodeling. The therapeutic effect of ACE2-hamscs is significant in hAMSCs group. It is considered that ACE2-hAMSCs may not only promote the paracrine effect of hAMSCs, The expression of pro-vascular growth factors GCP2 and IGF-1 can repair the injured pulmonary vascular endothelial cells and reduce the high pressure of pulmonary artery. Moreover, the high expression of ACE2 in hAMSCs is related to the regulation of RAS.