Abstract: Objective To investigate the effect of heme oxygenase-1 on the regulation polarization of macrophages during the development of atherosclerosis. Methods Cell experiments: RAW264.7 cells were induced by 100 ng/?L lipopolysaccharide (LPS) and 20 ng/?L interleukin 4 (IL-4) respectively, mRNA and protein were extracted 24 hours later. Real-time quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expression levels of HO-1, CD163, iNOS in induced macrophages. Western blotting was used to detect HO-1 protein expression levels. Animal experiments: ApoE-/- atherosclerosis mouse model was constructed. qPCR and Western blotting were used to detect the expression levels of HO-1 mRNA and protein in abdominal aorta of mice. Tissue immunofluorescence was used to detect the expression of HO-1 in M1 and M2 macrophages in aortic sinus. Results LPS and IL-4 successfully induced M1 and M2 macrophages; HO-1 expression in IL-4 induced macrophages were significantly higher than that in LPS and the control group. The expression of HO-1 in ApoE-/-mice was significantly higher than that in the C57BL / 6 control group (P <0.05). Colocalization expression of HO-1 and CD206 in aortic sinus was significantly higher than HO-1 and CD86. Conclusions HO-1 expression in M2 macrophages was significantly higher than M1, which plays a protective role in the development of arteriosclerosis.