Aim Human umbilical vein endothelial cells (HUVEC) were incubated with high homocysteine (Hcy) in vitro, establishing inflammatory damage model of vascular endothelial cell, after intervening with Diplacone, to observe the effect of Diplacone on HUVEC, and to explore the possible protective effect of Diplacone on vascular endothelial cell. Methods HUVEC were pretreated with different concentrations of Hcy, choosing the optimal damage concentration and time of Hcy. HUVEC were treated with different concentration of Diplacone for 2 hours then treated with Hcy for 12 h. The change of cell activity was detected by MTT method; Cell nucleus damage was detected by Hoechst33342 stain; Protein expression levels of vascular cell adhesion molecule-1 (VCAM-1) and P-seletin were detected by Western blot method. The above tests were used to show the protective effect of Diplacone on HUVEC induced by high Hcy. Results Compared with the normal group, the activity of the 2 mmol/L Hcy group was significantly lower (P<0.01), while Diplacone concentration was less than 10 μmol/L, Diplacone showed a concentration dependent on decreasing the damage of Hcy on HUVEC and decreased VCAM-1 and P-selectin protein expression that were increased by Hcy in HUVEC (P<0.01). Conclusion Diplacone has protective effect on endothelial injury induced by high Hcy in HUVEC.