Objective：To investigate the protective effect of aloperin on the apoptosis of human umbilical vein endothelial cells（HUVECs）induced by hypoxia/reoxygenation. Methods：HUVECs were cultured and randomly divided into the control group，the hypoxia/reoxygenation group，the aloperin（20，50 and 100 mg/L）pretreatment group and the aloperin+LY294002 group，and treated accordingly. Cell proliferation and apoptosis were detected by MTT assay and flow cytometry，respectively. Caspase-3 activity was detected by colorimetry，and protein expression of Bax，Bcl-2，Akt and p-Akt were detected by Western blot. Results：Aloperin reversed the decrease of proliferation and increase of apoptosis induced by hypoxia/reoxygenation in human umbilical vein endothelial cells（P < 0.05）. Aloperin alleviated the increase of Caspase-3 activity and Bax expression，and the downregulation of Bcl-2 induced by hypoxia/reoxygenation，and increased Bcl-2/Bax value（P < 0.05）. In addition，aloperin significantly upregulated p-Akt protein expression（P < 0.05），while the anti-apoptosis effect of aloperin against hypoxia/reoxygenation was significantly reversed by PI3K/Akt inhibitor LY294002（P < 0.05）. Conclusion：Aloperin could inhibit hypoxia/reoxygenation-induced apoptosis of HUVEC cells by activating the PI3K/Akt pathway.