Aim To investigate the effect of cytochrome P450 2J2 （CYP2J2） on atherosclerosis by overexpression of CYP2J2 in the cultured human umbilical vein endothelial cell （HUVEC） and human peripheral monocyte-derived foam cell model. Methods Recombinant pLVX-IRES-ZsGreen1-CYP2J2 lentiviral vectors were infected into HUVECs and human peripheral monocyte-derived foam cells. CYP2J2 expressions in cells were detected by reverse transcription polymerase chain reaction （RT-PCR） and Western blot. Cultured HUVECs were divided into control group, vehicle group （pLV group） and CYP2J2 overexpression group （pLV-CYP2J2 group）. Cell proliferation and migration were determined by MTS and Transwell assay. In addition, monocytes were isolated from the peripheral blood of patients with coronary heart disease by Ficoll-Hypaque density gradient centrifugation and plastic adsorptive process. The isolated cells were induced and stimulated by phorbol-12-myristate-13-acetate （PMA） at concentration of 50 nmol/L for 48 h to transfer them into macrophages, then adding oxidized low density lipoprotein （ox-LDL） at a final concentration of 80 mg/L to make the cells transformed into foam cells. Cells were also divided into control group, pLV group and pLV-CYP2J2 group, all of them were collected in 48 h after the virus transfection. Intracellular lipid droplets and total cholesterol were detected by oil red O staining and the total cholesterol assay kit. Results The results of RT-PCR and Western blot demonstrated that CYP2J2 mRNA and protein expression were significantly increased in both HUVECs and foam cells after pLV-CYP2J2 virus infection. Compared with the control group and pLV group, pLV-CYP2J2 infection significantly enhanced the cell proliferation of HUVECs in 24, 48, 72 h, and the cell migration in 48 h, but there was no significant difference in cell proliferation in 12 h. In addition, in human peripheral monocyte-derived foam cell model, pLV-CYP2J2 infection significantly reduced the number of foam cells, oil red lipid droplets and total cholesterol content. Conclusion CYP2J2 can be overexpressed in HUVECs and human peripheral monocyte-derived foam cells, which promotes the proliferation and migration of HUVECs, and reduces the formation of foam cells, so it suggests that CYP2J2 has the function of anti-atherosclerosis.