Abstract: Objective：To investigate the effect of hydrogen sulfide (H2S) on pulmonary hypertension (PAH) induced by monocrotaline (MCT) and the underlying mechanisms related to endothelial-to-mesenchymal transition (EndMT). Methods：A total of 40 male SD rats were randomly divided into control group, MCT group, sodium hydrosulfide (NaHS) group, and propargylglycine (PAG, H2S synthesis inhibitor) group. The rats in MCT group, NaHS group, and PAG group were given an intraperitoneal injection of MCT (60 mg/kg) to induce PAH. Seven days after MCT injection, NaHS (1 mg·kg-1·d-1, NaHS group), PAG (10 mg·kg-1·d-1, PAG group), or 0.9% saline (MCT group) were intraperitoneally administered within 14 d. Twenty-one days after MCT injection, pulmonary arterial pressure was tested by right heart catherization. Then, all the rats were sacrificed and pulmonary artery remodeling and pulmonary EndMT were examined. Meanwhile, human pulmonary artery endothelial cells (HPAECs) were pretreated with saline or NaHS (50, 100, and 200 μmol/L) for 2 h, and then stimulated with TGF-β1 (10 ng/mL) for 1 h, 3 d, or 10 d respectively to observe the expression of Snail, EndMT, and cell morphological changes. Results：Compared with the control group, pulmonary systolic pressure (PASP), mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), pulmonary arteriolar wall thickness, α-smooth muscle actin (α-SMA), and Snail in the lung tissue significantly increased in the MCT group, whereas the expression of VE-cadherin was significantly decreased (P<0.05). NaHS intervention significantly reversed the trend while PAG aggravated it (P<0.05). In vitro results showed that TGF-β1 stimulation significantly upregulated the ratio of spindle cells, the expression levels of α-SMA and Snail in HPAECs (P<0.05), and decreased the expression level of VE-cadherin (P<0.05). NaHS pretreatment inhibited TGF-β1-induced morphology changes of cell, and expression levels of α-SMA, VE-cadherin, and Snail in a dose-dependent manner. Conclusions：Hydrogen sulfide could alleviate PAH induced MCT, its mechanism may correlate with its effect on pulmonary artery EndMT.