The East Asian respond with a marked facial flushing and mild to moderate symptoms of intoxication after drinking the amounts of alcohol that has no detectable effect on European. The alcohol sensitivity in Orientals is due to a delayed oxidation of acetaldehyde by an atypical aldehyde dehydrogenase ALDH2⁎487Lys, which is resulted from a structural mutation in gene ALDH2. The atypical ALDH2⁎487Lys allele has been associated with various phenotypic statuses, such as protective against alcohol dependence and the risk of alcohol-related digestive tract cancers. Here, we have examined this SNP, adjacent four non-coding SNPs, and one downstream STRP on ALDH2 gene, in total of 1072 unrelated healthy individuals from 14 Chinese populations and 130 Indian individuals. Five major haplotypes based on five SNPs across the ALDH2 gene 40 kb were found in all East Asian populations. The frequencies of the ancestral haplotype GCCTG and the East Asian special haplotype GCCTA containing the atypical ALDH2⁎487Lys allele were 44.8% and 14.9%, respectively. The frequency of the atypical ALDH2⁎487Lys allele or the East Asian specific haplotype GCCTA is high in Yunnan, South coastal, east coastal of China, and decreased gradually toward inland China, West, Northwest and North China. Combined with demographic history in East Asian, our results showed that the presence of ALDH2⁎487Lys allele in peripheral regions of China might be the results of historical migration events from China to these regions. The origin of ALDH2⁎487Lys could be possibly traced back to ancient Pai-Yuei tribe in South China.