Atherosclerosis is a leading cause of vascular disease worldwide. Paeonol has been reported to have therapeutical potential in atherosclerosis. The aim of this study is to explore the effect of paeonol on oxidized low-density lipoprotein (ox-LDL)-induced endothelial cells injury and the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were treated with ox-LDL (100 μg/ml) to mimic atherosclerosis in vitro. The cell viability, proliferation, and apoptosis were assessed by cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry, respectively. The angiogenesis was detected by tube formation assay. The levels of inflammatory factor were measured by enzyme-linked immunosorbent assay (ELISA). In addition, the levels of Fe