Pulmonary vascular remodelling is a common feature among the heterogeneous disorders that cause pulmonary arterial hypertension (PAH), and pulmonary arterial smooth muscle cells (PASMCs) proliferation impact the long‐term prognosis of the patient. Isoquercitrin (IQC) is a flavonoid with anti‐oxidative, anti‐inflammatory and anti‐proliferative activations. This study aimed to investigate whether IQC could prevent PASMCs proliferation and vascular remodelling in monocrotaline (MCT) induced PAH. Male Wistar rats were administered with Vehicle or 0.1% IQC maintain feed after MCT (40 mg/kg) injection. Haemodynamic changes, right ventricular hypertrophy and lung morphological features were assessed 3 weeks later. MCT‐induced PAH, pulmonary vascular remodelling and PASMCs proliferation in Vehicle‐treated rats. IQC reduced the right ventricle systolic pressure (RVSP), the ratio of RV/LV+S and the RV hypertrophy. IQC significantly alleviated the expression of proliferating cell nuclear antigen (PCNA), smooth muscle α‐actin (α‐SMA), and the percentage of fully muscularized small arterioles. In vitro studies, PASMCs were pretreated with IQC and stimulated with platelet‐derived growth factor (PDGF)‐BB (20 ng/mL). IQC suppressed PDGF‐BB‐induced PASMCs proliferation and caused G0/G1 phase cell cycle arrest. IQC downregulated the expression of Cyclin D1 and CDK4 as well as inhibited p27Kip1 degradation. Meanwhile, IQC negatively modulated PDGF‐BB‐induced phosphorylation of PDGF‐Rβ, Akt/GSK3β and ERK1/2. IQC ameliorated MCT‐induced pulmonary vascular remodelling via suppressing PASMCs proliferation and blocking PDGF‐Rβ signalling pathway.