Abstract: Objective To investigate the effect of heme oxygenase-1 on the regulation polarization of macrophages during the development of atherosclerosis. Methods The mRNA and protein of RAW264.7 cells were extracted by inducing RAW264.7 cells with 100 mg/L lipopolysaccharide (LPS) and 20 mg/L interleukin-4 (IL-4) for 24 h respectively. The expression of HO-1, CD163 and Inducible nitric oxide synthetase (iNOS) mRNA in macrophages induced by LPS and IL-4 was detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the expression of HO-1 protein in macrophages induced by LPS and IL-4 was detected by Western blot. The changes of aortic plaque area after apoE knockout (ApoE^-/-) mice were detected by gross Oil Red O staining, and HO-1 mRNA and protein expression were detected by RT-qPCR and Western blot. The colocalization of HO-1 with macrophages of pro-inflammatory type (M1) and anti-inflammatory type (M2) was detected by tissue immunofluorescence. Results LPS and IL-4 successfully induced M1 and M2 macrophages. The expression of HO-1 in macrophages induced by IL-4 was significantly higher than that in LPS and control group (P<0.05). The establishment of atherosclerosis model was successful. The expression of HO-1 in ApoE ^-/- mice was significantly higher than that in C57BL/6 control group (P<0.05). The colocalization expression of HO-1 and CD206 in aortic sinus was significantly higher than that in HO-1 and CD86. Conclusions HO-1 expression in M2 macrophages is significantly higher than M1 macrophages, which plays a protective role in the development of arteriosclerosis.