Aim To investigate whether the myocyte enhancer factor 2(MEF2) gene family was subjected to strong natural selection in different human populations,and reveal its roles in pathogenesis,and simultaneously provide a new vision and a novel entry point for research on the pathogenesis mechanism of cardiovascular diseases. Methods A measure of population differentiation(Fst) was calculated between the Han Chinese(CHB),Europe Caucasion(CEU),Yoruba Nigerian(YRI) and Japanese(JPT) through using the SNP frequency data published by the Human HapMap projects,and phylogenetic analysis was performed. Results Many SNPs in MEF2A gene region were observed with a high Fst(Fst>0.3) between YRI and CHB,YRI and CEU,and YRI and JPT.However,no SNPs with a high Fst were observed between CHB and CEU,CHB and JPT,and CEU and JPT.In MEF2B,MEF2C and MEF2D gene regions,all SNPs except that in MEF2D showed a low Fst between any two populations of CHB,CEU,YRI and JPT.These results suggested that MEF2A gene was subjected strong natural selection during that human migrated worldwide from Africa,and it must have played key roles in the process that human adapted to new environment. Conclusion MEF2A gene must has been subjected to diversifying selection during the divergence of human populations,and the diversity in SNP frequency between different human populations might have been cumulated in the course of adaptation to environment.