Abstract: Objective To determine the effects of tanshinone ⅡA (Tan ⅡA) on the injury of human umbilical vein endothelial cells (HUVECs), and its relationship with oxidative stress regulation. Methods HUVECs were cultured in high glucose medium to investigate the role of Tan ⅡA in vitro. The cell viability was measured by CCK-8 assay. The levels of P38, p-P38, caspase 3 and cleaved caspase 3 were investigated by Western blot. Reactive oxygen species/superoxide anion (ROS/O^-₂) fluorescence probe was used to detect the changes of ROS and O^-₂ in each group. Results High glucose treatment induced decreased HUVECs viability, enhanced the expression of ROS and O^-₂, and increased the levels of p-P38 and cleaved caspase 3. Furthermore, exposure to Tan ⅡA resulted in decreases in HUVEC viability induced by high glucose, inhibited the expressions of ROS and O^-₂, and blocked P38 phosphorylation and the activation of caspase 3. Conclusions High glucose can cause apoptosis in HUVECs, and Tan ⅡA can relieve HUVECs apoptosis induced by high glucose through inhibiting the ROS/P38 MAPK signaling pathway.