Background Abnormal apoptosis of pulmonary artery smooth muscle cells (PASMCs) is an important pathophysiological process in the pulmonary artery structural remodeling and pulmonary hypertension. We investigated possible effect of endogenous hydrogen sulfide (H_2S) on apoptosis of PASMCs during the development of pulmonary hypertension induced by high pulmonary blood flow.Methods Thirty-nine male Sprague-Dawley rats were randomly assigned to 4-week control, 4-week shunt, 4-week shunt+propargylglycine (PPG), 11-week control, 11-week shunt and 11-week shunt+sodium hydrosulfide (NaHS) groups. Rats in 4-week shunt, 4-week shunt+PPG, 11-week shunt and 11-week shunt+NaHS groups underwent an abdominal aorta-inferior vena cava shunt. Rats in 4-week shunt+PPG group were intraperitoneally injected with PPG, an inhibitor of endogenous H_2S production, for 4 weeks. Rats in 11-week shunt+NaHS group were intraperitoneally injected with NaHS, a H_2S donor, for 11 weeks. Lung tissue H_2S was evaluated by sulfide-sensitive electrode. Apoptosis of PASMCs were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). Expressions of Fas, bcl-2 and caspase-3 in the PASMCs were analyzed with immunochemical staining.Results Four weeks after the shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased (P<0.01), but expression of bcl-2 increased significantly (P<0.01). PPG administration further inhibited the apoptosis of PASMCs, downregulated the expression of Fas and caspase-3 (P <0.01), but increased the expression of bcl-2 (P<0.01). After 11 weeks of shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased (P <0.01), but expression of bcl-2 increased obviously (P <0.01). NaHS administration significantly increased the apoptosis of PASMCs, upregulated the expression of Fas and caspase-3, but inhibited the expression of bcl-2.Conclusions H_2S induces the apoptosis of PASMCs in the development of high pulmonary blood flow-induced pulmonary hypertension by activating the Fas pathway and inhibiting the bcl-2 pathway.