ABSTRACT Objective: To investigate the protective effect of Tadehaginoside on vascular endothelial cell injury induced by reactive nitrogen. Methods: MTT colorimetry was used to detect the effect of Tadehaginoside on the survival rate of EA.hy 926 endothelial cells in the concentration range of 5～160 μmol/L; 1 h after pre-administration of Tadehaginoside, 0.5 mM GSNO was given to damage endothelial cells. Detect the mitochondrial specific factors COX-1, ND-1 and inflammatory factor IL-1β of EA.hy 926 cells damaged by GSNO by Real time-PCR method gene intervention. At the same time, Western blot was used to detect the changes in Bax and Bcl-2 protein expression. The mitochondrial membrane potential kit (JC-1) was used to detect the change of Tadehaginoside on the mitochondrial membrane potential after GSNO induced EA.hy 926 cell injury. Results: The results of the MTT method showed that Tadehaginoside had no obvious cytotoxicity on EA.hy 926 cells in the range of 5～160 μmol/L, and the optimal protective concentration of the drug was 40 μmol/L. Western Blot method showed that BAX protein expression increased in a time-dependent manner after GSNO damaged EA.hy 926 cells over time, while Bcl-2 protein expression was the opposite. Real time-PCR results showed that Tadehaginoside can significantly up-regulate COX-1 gene (P < 0.05), and can significantly inhibit GSNO induced ND-1 (P < 0.05) and IL-1β gene up-regulation (P < 0.01). At the same time, the results of JC-1 showed that Tadehaginoside could significantly protect the mitochondrial membrane potential from GSNO damage. Conclusion: The GSNO damage model may induce the increase of Bax and other pro-apoptotic proteins through mitochondrial DNA damage and reduce the expression of anti-apoptotic factor Bcl-2. Tadehaginoside has a certain protective effect on endothelial cell mitochondrial damage induced by reactive nitrogen, and its mechanism is related to inhibiting the expression of ND-1 and IL-1β genes and up-regulating the expression of COX-1 genes.