Objective To study the protective effect of Panax notoginseng saponins (PNS) and its components Rg1 and Rb1 on oxygen-glucose deprivation/ reoxygenation ( OGD/ Reox)-induced tight junction damage. Methods Anaerobic box were used to induce OGD in HUVEC cells for 6 h followed by reoxygenation for 24 h. Transepithelial/endothelial electrical resistance (TEER) and cell permeability were detected, immunefluorescence was used to observe the ZO-1 and claudin-5 protein expression. Results PNS 20, 40 mg/ L and ginsenoside Rb1 significantly inhibited the OGD/Reox-induced decreased tight junction resistance, and the increased cell permeability (P < 0.05). PNS 20, 40 mg/ L and ginsenoside Rb1 partly restored the inter-cellular tight junctions which were regularly arranged on the cell membrane, and the cells displayed cobble stone-like arrangement. Conclusions PNS ameliorates ischemia-induced vascular endothelial cell tight junction damage via MMP-9 and VEGF/ VEGFR2 signaling pathway. Rb1 is one of the effective monomer components.