Objective  To investigate the possible effect and the underlying mechanism of isoliquiritigenin (ISL) on hypoxic pulmonary hypertension（HPH）through observation of the changes of pulmonary artery pressure, vascular remodeling, and right ventricular hypertrophy in a chronic hypoxia rat model. Methods  Thirty male Sprague-Dawley rats were randomly divided into 3 groups (10 rats per group): normoxia group, hypoxia group and hypoxia group treated with ISL. For hypoxia group treated with ISL, rats were injected intraperitoneally ISL［10 mg/（kg·day), dissolved in 0.5% DMSO］. For normoxia and hypoxia groups, rats were injected intraperitoneally equal amount of 0.5% DMSO. After 4 weeks hypoxia exposure, the right ventricle systolic pressure (RVSP) was recorded using Power Lab Software. The weight ratio of ［right ventricle (RV) / left ventricle +septum (LV+S) ］ was calculated as an index of RV hypertrophy. After HE staining, the percent medial wall thickness (WT%) and percent medial wall area (WA%) in small pulmonary arteries were determined. The content of superoxide dismutase (SOD) and malonaldehyde (MDA) were measured using commercial kits. NADPH oxidase 4(NOX4) mRNA levels in lung tissues were measured by Real-time PCR. Results  The average RVSP, ratio of RV/LV+S, WT%, and WA% of hypoxia group were increased significantly compared with the normoxia group (P<0.01). However, the average RVSP, ratio of RV/LV+S, WT%, and WA% of hypoxia treated with ISL group were much lower than those of hypoxia group (P<0.01). In addition, the result showed that hypoxia decreased the level of SOD, companied with an increased level of MDA both in lung tissue and in serum (P<0.01). ISL treatment elevated the level of SOD and reduced the level of MDA (P<0.01). Real-time PCR result showed ISL obviously down-regulated the NOX4 mRNA levels in lung tissues (P<0.01). Conclusion  ISL may have beneficial effects on the HPH and these effects may be related to the inhibition of the oxidative stress caused by hypoxia.