Abstract: OBJECTIVE To investigate the protective effect of epalrestat on pulmonary vascular remodeling in rats with monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH), and explore whether the effect was related to inhibiting the expression of TGF-β1 and aldose reductase(AR). METHODS Forty-eight rats were randomly divided into four groups, with 12 rats per group, as follows:control group, MCT group, epalrestat 50 mg·kg^-1 group and epalrestat 100 mg·kg^-1 group. PAH model was established by subcutaneous injection of MCT at the dose of 60 mg·kg^-1. After 4 weeks of continuous gavage, the Cournand catheter with a diameter of 0.5 mm was slowly pushed to the ventricle and pulmonary artery from the right external jugular vein. At the end of experiment, the right ventricular systolic pressure(RVSP) and mean pulmonary artery pressure(mPAP) were monitored by MedLab system. Pathological changes and collagen deposition of pulmonary artery was observed by HE staining and Masson respectively. The aldose reductase(AR) expression in pulmonary artery was measured by immunohistochemistry. The expression of proliferating cell nuclear antigen(PCNA), collagen I, TGF-β1 and AR were analyzed by qPCR and Western blot. RESULTS Epalrestat treatment for 4 weeks attenuated RVSP, mPAP and pulmonary vascular remodeling of PAH rats. Furthermore, pulmonary arteries collagen accumulation and PCNA and collagen I expression were both significantly suppressed by epalrestat treatment. The expression of TGF-β1 and AR were obviously decreased in pulmonary arteries from PAH rats with epalrestat treatment. CONCLUSION These findings demonstrate that epalrestat ameliorates pulmonary vascular remodeling of PAH rats through down-regulating of TGF-β1and AR expression.