Atherosclerosis (AS) is a common pathological basis for the development of various cardiovascular and cerebrovascular diseases, however, currently, no effective treatment against AS has been established. It has previously been suggested that intravascular cytochrome P450 (CYP) oxidase is involved in the pathogenesis of AS. The present study investigated the role of cytochrome P450, family 2, subfamily J, polypeptide 2 (CYP2J2), the most common subtype of CYP oxidase in the human body, in the occurrence and development of AS. CYP2J2 was overexpressed in human umbilical vein endothelial cells (HUVECs), human arterial smooth muscle cells (HASMCs), and human peripheral monocyte‑derived foam cells by lentiviral infection. The mRNA and protein levels were measured by reverse‑transcription quantitative polymerase chain reaction and western blotting, respectively. Cell proliferation and migration were determined by MTS and Transwell assays, respectively. Furthermore, lipid accumulation was detected with Oil red O staining. The concentrations of total and free cholesterol were measured using a quantitation kit. Following lentiviral infection, CYP2J2 was successfully overexpressed in HUVEC, HASMC and foam cells. CYP2J2 overexpression promoted proliferation and migration in HUVECs and suppressed these actions in HASMCs. In addition, it suppressed oxidized low‑density lipoprotein‑induced foam cell formation. In conclusion, it was hypothesized that CYP2J2 may have a protective role in AS, as proliferation of HASMCs and the formation of foam cells are notable characteristics of AS.