To test the hypothesis that micro-opioid receptor (OPRM1) gene might be involved in the prevalence of obesity, a population-based association study was carried out in Uyghur population. Overall 10 tagging single-nucleotide polymorphisms (tSNPs) in OPRM1 gene were genotyped. We showed that genotypes of rs1799971 in exon 1, and rs514980 and rs7773995 in intron 1 were significantly associated with the BMI. The BMI significantly decreased by the copy of minor allele carriers of rs1799971 which is a nonsynonymous functional polymorphism, whereas the BMI significantly increased by the copy of minor allele carriers of rs514980 and rs7773995. Subsequently, subjects were subsequently divided into case (BMI >or= 28) and control group (BMI < 24). Significant associations were again observed at rs1799971, rs514980, and rs7773995, regardless of controlling for covariates age and gender or not. The stronger evidence for association was found under the additive model for each of the three SNPs. The per-allele odds ratio of the minor allele for obesity was 0.75 (95% confidence interval 0.58-0.96, P = 0.023) for rs1799971, 1.68 (95% confidence interval 1.14-2.49, P = 0.009) for rs514980, and 1.80 (95% confidence interval 1.14-2.85, P = 0.012) for rs7773995, respectively. Our observations give the evidence that OPRM1 gene is involved in the prevalence of obesity in Uyghurs.