Aim To investigate the role of DNA methylation of Rap1A in Hcy-induced RAW264.7 cell proliferation. Methods RAW264.7 cells in logarithmic growth phase were divided into control group (Control) and Hcy treated groups with different concentrations (0,0, 0,0, 100 μmol/L Hcy). Cell viability was detected by XTT to screen optimal intervention time and concentration of Hcy after cells were treated for 24 hours. Edu test was used to analyze cell proliferation. The expression levels of Rap1A mRNA and protein were measured by qRT-PCR and Western blot respectively. Methylation-specific PCR (MSP) was used to detect the change of Rap1A promoter region. The changes of Rap1A were examined by immunofluorescence staining. Rap1A interference adenovirus was transfected into RAW264.7 cells and stimulated with Hcy to detect the changes of mRNA and protein levels of Rap1A and cell proliferation. Results Compared with control group, the cell viability was enhanced after cells were treated with different concentration of Hcy, which was the most obvious when cells were treated by 100 μmol/L Hcy (P＜0.01), as well as cell proliferation(P＜0.01). But there was no time and concentration dependence. After Hcy stimulation, the expression of mRNA and protein of Rap1A increased significantly(P＜0.01). The result of MSP revealed that the methylation level of Rap1A promoter region was decreased (P＜0.01). Interfering with the expression of Rap1A can partially reverse the proliferation of cells induced by Hcy (P＜0.01). Conclusion DNA hypomethylation of Rap1A promoter region may play an important role in macrophage proliferation induced by Hcy.