Objective To determine the effect of hydrogen sulfide donor, sodium hydrosulfide (NaHS), on caveolin-1 (Cav-1) expression in pulmonary artery smooth muscle cells from hypoxic rats. Methods The chronic hypoxic rat model was established by intermittent normobaric hypoxia exposure. The hypoxic rat pulmonary artery smooth muscle cells (PASMCs) were cultured under mixed gas conditions. Thirty-two Sprague-Dawley (SD) rats were randomly and equally divided into four groups (normoxia group, hypoxia group, normoxia＋NaHS group and hypoxia＋NaHS group). The pulmonary arteriole intima-media thickness, muscularization and PASMCs proliferation was measured by immunohistochemical assay. Reactive oxygen species (ROS) was assessed by fluorescent probe assays. Western blotting was used to detect the protein expression of Cav-1. Results Compared with control rats, right ventricular systolic pressure (RVSP), right ventricular mass index (RVMI), medial wall thickness, fully muscularized vessels and proliferation of PASMCs were significantly enhanced in response to hypoxia. The level of ROS was significantly higher and the expression of Cav-1 was decreased in the PASMCs of hypoxia group than in control groups. NaHS treatment resulted in improvement of pulmonary arterial blood flow, alleviation of medial wall thickness, inhibition of PASMCs proliferation, decrease of ROS production, and enhancement of Cav-1 protein expression. Conclusion NaHS treatment alleviates pulmonary vascular structural remodeling in chronic hypoxic rats by decreasing ROS production, up-regulating the expression of Cav-1, and inhibiting PASMCs proliferation.