Abstract: Objective To evaluate the effect of overexpression of microRNA-124 （miR-124） on pulmonary vascular remodeling, and to unravel the potential mechanism in rats with pulmonary arterial hypertension （PAH）. Methods In the monocrotaline （MCT）-induced PAH rat models, intratracheal infusion of miR-124 carried by adeno-associated virus （AAV） was performed. The right ventricular systolic blood pressure （RVSP）, mean systolic arterial pressure and heart rate were recorded. The expression level of miR-124 in lung tissues of rats was detected by real-time quantitative PCR. The histological morphology of pulmonary arterioles was observed by van Gieson staining. The ratios of medium to outside diameter of pulmonary arterioles with vessel diameters in 25-50 μm and 51-100 μm were calculated. The expression levels of IL-6 and p-STAT3 protein in lung tissues were detected by Western blot. Results The expression level of miR-124 was down-regulated in pulmonary tissues of rats with PAH. RVSP was significantly decreased, the ratios of medium to outside diameter of pulmonary arterioles were significantly attenuated, and the expression levels of IL-6 and p-STAT3 proteins were significantly down-regulated by overexpression of miR-124. Conclusion AAV-mediated overexpression of miR-124 can significantly reduce RVSP and pulmonary vascular remodeling in rats with PAH, probably by down-regulating the expression levels of IL-6 and p-STAT3.