BACKGROUND: Adiponectin, an adipocyte-secreted protein, is known to modulate insulin sensitivity, glucose homeostasis and the development of atherosclerosis. Recently, several single nucleotide polymorphisms (SNPs) in the adiponectin gene have been reported to be associated with type 2 diabetes and components of the insulin resistance syndrome. METHODS: The frequencies of SNP T45G and G276T of the adiponectin gene was examined in 493 unrelated type 2 diabetic and 136 non-diabetic control Korean subjects. The clinical characteristics and plasma adiponectin levels of the subjects were compared within these genotypes. RESULTS: The T allele at SNP45 was significantly more frequent in the type 2 diabetes than in the control subjects (71.6 vs. 64.3%, p=0.013). The subjects with the G/G genotype of SNP45 were at reduced risk for type 2 diabetes (OR: 0.495, 95% CI 0.246-0.995, p=0.048) compared with those having the T/T genotype. However, there were no statistically significant differences in allele the frequencies (G frequency in the control vs. the diabetic group 73.9 vs. 68.9%, p=0.106) and genotype frequencies at SNP276 between groups. The subjects with the T/T genotype at SNP45 had higher a body mass index (24.6+/- 3.1 vs. 24.1+/-2.8 kg/m2, p=0.036) and serum triglyceride levels (2.03+/-1.31 vs. 1.87+/-1.38 mmol/1, p=0.041) than the T/G+G/G genotypes in the diabetic group. Those with the T/T genotype also had lower plasma adiponectin levels than those without T/T genotype at SNP45 in the control group (6.11+/-3.10 vs. 8.24+/-4.24 g/mL, p=0.043). There was a similar trend in diabetic group, but this did not reach statistical significance (4.32+/-2.81 vs. 4.96+/-3.26 g/mL, p=0.097). The SNP276 had no association with the clinical features of insulin resistance or plasma adiponectin level. CONCLUSION: The T/T genotype of SNP45 in the adiponectin gene was associated with a low adiponectin level, high body mass index, the serum triglyceride level and risk of type 2 diabetes mellitus. The SNP276 in the adiponectin gene may not be an important determinant of insulin resistance or type 2 diabetes in Korean subjects.