Background: An important pathogenic mechanism in the development of pulmonary arterial hypertension (PAH) is hypothesized to be the pulmonary vascular remodeling, in which cancer-like pulmonary arterial smooth muscle cells (PASMCs) proliferation and perivascular inflammation play an important role. Ginsenoside compound K (G-CK) exhibits anticancer and anti-inflammation properties. However, whether or not G-CK could protect against PAH in rats is still unknown. Objective: The aim was to investigate whether or not G-CK attenuates PAH, if so, to elucidate the molecular mechanisms underlying its effects. Methods and Results: we established PAH rat models by left pneumonectomy combined with monocrotaline, and PAH rats were treated G-CK in the prevention (on 7 th day) and reversal group (on 21th day) respectively. The weekly body weight, the survival rate, mean pulmonary arterial pressure and right ventricle hypertrophy index of prevention group and reversal group improved to varying degrees. Hematoxylin and eosin and elastic Van Gieson staining of lung tissue showed that the increased of wall thickness, vescular occlusion score and the degree of neointimal proliferation in the model group were mitigated by G-CK. Immunohistochemical analysis of Ki67 and α-smooth muscle actin showed that G-CK suppressed proliferation of PASMCs and muscularization compared with model group. Moreover, G-CK inhibited NF-κB/Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signalling and reduced IL-18, TNF‐α, IL‐6, and IL‐1β in lung tissue by western blot.