In conclusion, we show that CRMP2 plays a role in macrophage polarization of M1 phenotype and CRMP2 RNAi resulted in a switch of M1 to M2 macrophages not only in vitro but also in ApoE−/− mice with MI, leading to an promoted inflammation resolution, enhanced cardiac function recovery and decreased mobility after MI. This evidence concerns the gene APOE and myocardial infarction.