Adiponectin gene polymorphisms have recently been reported to be associated with obesity, insulin sensitivity, and the risk of type 2 diabetes. We examined a T94G polymorphism of the adiponectin gene in 245 ostensibly normal nondiabetic subjects. The G allele frequency was lower among subjects with higher BMI (=27) than in those with lower BMI. BMI was inversely correlated with the dose of G allele. Multivariate linear regression analyses showed that the adiponectin genotypes were significantly related to BMI after adjusting for age and gender. The dose of the G allele was associated with a reduction of approximately 1.12 kg/m ² in BMI. We further found that the relative mRNA levels of G allele were consistently higher than those of T allele in the omental adipose tissue from 21 heterozygous subjects. Finally, we observed that the expression levels of adiponectin affected insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In conclusion, the allele-specific differential expression of this common polymorphism could be responsible for its biological effects observed in this and the other studies.