CXCL12 and endothelial dysfunction: To investigate the ameliorative effect of polydatin on PAH injury, this study established MCT-induced PAH related injury, including right ventricular compensatory hypertrophy, CXCL12/CXCR4 dominated pro-inflammatory environment, impairment of HIF-2ɑ/Arg1 pathway, endothelial dysfunction, and vascular remodeling.