Aim To study the effects of homocysteine （Hcy） on methylation of Bcl-2 in human umbilical endothelial cells （HUVEC）. Methods After human umbilical endothelial cells were treated with different concentrations of Hcy for 48 h, MTT was used to measure the reproduction of human umbilical endothelial cells and IC50 concentration of Hcy, the flow cytometry assay was used to detect the rate of cell apoptosis, the expressions of Bcl-2 mRNA level were analyzed by fluorescence quantitative PCR, the methylation of Bcl-2 promoter region methylation level was determined by nest touch-down PCR combined methylation specific PCR （MSP）. Results The proliferation of human umbilical endothelial cells was inhibited by Hcy in a dose-independent manner, the OD value decreased from 0.99±0.05 to 0.28±0.03（P<0.01）. Compared with control group, the rate of apoptosis in human umbilical endothelial cells increased from 2.30%±0.60% to 16.40%±0.73% （P<0.01）, the expressions of Bcl-2 mRNA were significantly depressed （P<0.01）, the Bcl-2 promoter region methylation levels in experimental group were significantly reduced （P<0.05）. Conclusions Increasing endothelial cell apoptosis by decreasing Bcl-2 promoter region methylation level and reducing expression of Bcl-2 may play an important role in the pathogenesis of Hcy induced atherosclerosis.