Objective: The present study was to investigate the effects of sesamin on pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertension (PH) of rats.Method: PH rats were induced by a single injection of monocrotaline (mg·kg-1, sc) and were administered sesamin (50 and 100 mg.kg-1.d-1) for 4 weeks.At the end of experiment, the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored via the right jugular vein catheterization into the right ventricle.Right ventricle (RV) to left ventricle (LV) + septum (S) and RV to tibial length were calculated.Small pulmonary vessels change was observed by HE staining.Massons trichrome stain was used to demonstration collagen deposition.The alpha-smooth muscle actin (α-SMA) expression in small pulmonary vessels was measured by immunohistochemisty.The Total antioxidative capacity (T-AOC) and malondialdehyde (MDA) levels in pulmonary arteries were determined according to the manufacturers instructions.The expression of collagen Ⅰ, NOX2 andNOX4 was analysed by real-time PCR and Western blot.Result: The results showed that sesamin treatment for 4 weeks attenuated RVSP, mPAP and right ventricular remodeling index (RV/LV+S and RV/Tibial length) of PH rats induced by monocrotaline.Furthermore, monocrotaline-induced pulmonary arteries collagen accumulation and collagen Ⅰ and α-SMA expression were both significantly suppressed by sesamin.Furthermore, the expressions of NOX2, NOX4 and MDA content were obviously decreased, while the T-AOC was significantly increased in pulmonary arteries from PH rats with sesamin treatment.Conclusion: These findings demonstrate that sesamin ameliorates pulmonary vascular remodeling of PH induced by monocrotaline in rats through its down-regulating of NO2 and NOX4 expression and reducing oxidative stress injury.