Aim To investigate the effect of curcumin on the progression of atherosclerosis and macrophage polarization in vivo. Methods The apolipoprotein E deficient (ApoE－/－) mice were fed with high fat diet to establish atherosclerosis model. The aortas were isolated for haematoxylin and eosin, masson trichrome, picrosirus red, oil red O and immunofluorescence staining. Inducible nitric oxide synthase (iNOS) and CD206 were utilized as biomarkers of M1 and M2 phenotypes, respectively. Quantitative real-time polymerase chain reaction (PCR) was carried out to examine the gene expression of inflammatory factors. Results Curcumin significantly decreased atherosclerotic burden and plaque vulnerability in the experimental atherosclerosis model. Furthermore, curcumin decreased the ratio of M1/M2 macrophages together with the gene expressions of pro-inflammatory interleukin 1beta (IL-1β), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), but promoted the levels of anti-inflammatory cytokines IL-10, Ym1, Fizz1 in the atherosclerotic plaque. Conclusion Curcumin could alleviate the progression of atherosclerosis by inhibiting macrophage polarizing towards M1 phenotype as well as inflammatory response.