Aim In this experiment, human umbilical vein endothelial cells were induced by HHcy in vitro, and the inflammatory damage model of vascular endothelial cells was established, the effect of Diplacone on human umbilical vein endothelial cells was observed by pretreatment with Diplacone, and further explored the possible protective mechanism of Diplacone on vascular endothelial cells. Methods Human umbilical vein endothelial cells were used as the research object and were preincubated by Diplacone with different concentrations for 2 h, then 2 mmol/L Hcy was added to continue incubating for 12 h, changes of cell apoptosis rate were detected by flow cytometry; the level of oxidative stress was detected by ROS cell rate, MDA, GSH-Px,SOD in cells; protein expression and mRNA levels of NF-κB were detected by Western blot. Results Compared with control group, cell apoptosis rates were increased, oxidative stress indexes including ROS cell rate and MDA were increased and the activities of GSH-Px and SOD were decreased; the expression of NF-κB protein and mRNA increased significantly. After human umbilical vein endothelial cells were preincubated by Diplacone with different concentrations, compared with Hcy model group, cell apoptosis rates were decreased in 0.1～10 μmol/L; oxidative stress indexes including ROS cell rate and MDA were decreased and the activities of GSH-Px and SOD were increased; the expression of NF-κB protein and mRNA decreased significantly in 0.1～10 μmol/L Diplacone. Conclusion Diplacone can inhibit Hcy-induced endothelial damage in human umbilical vein endothelial cells and the mechanism may be through reducing oxidative stress and inhibiting the activity of NF-κB signaling pathway to reduce cell apoptosis rate and inhibit cell apoptosis.