Pulmonary artery hypertension (PAH) is a chronic and deadly disease, for which effective medical treatments are lacking. Here, we investigated whether 2R, 3R-dihydromyricetin (DHM) could prevent monocrotaline (MCT)induced PAH in rats. The MCT-injected rats were treated with normal saline or DHM (100 mg/kg body weight/d) for 4 weeks, followed by measurements of right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), pulmonary arterial remodeling (PAR), and expression levels of IL-6, TNF-alpha, and IL-10. In vitro, we assessed the role of DHM on IL-6-induced migration of primary human pulmonary arterial smooth muscle cells (HPASMCs). We found that DHM treatment attenuated changes in RVSP, RVHI, and PAR in MCTinjected PAH rats. The observed increase of IL-6 levels in PAH rats was inhibited by DHM treatment. In vitro, DHM pretreatment reduced IL-6-induced HPASMC migration. Furthermore, MCT-and IL-6-mediated increases in MMP9 and P-STAT3 (tyr705) PY-STAT3 levels were suppressed by DHM treatment in vivo and in vitro. These results suggest that DHM could prevent MCT-induced rat PAH and IL-6-induced HPASMC migration through a mechanism involving inhibiting of the STAT3/MMP9 axis.