Adiponectin is an adipocyte-secreted protein that is known to modulate insulin sensitivity and glucose homeostasis. A number of genetic variations have been studied. Among them, two single-nucleotide polymorphisms (SNP45T>G, SNP276G>T) showed an association with type 2 diabetes in the Japanese population. In this study, we examined the association between these SNPs and risk factors of type 2 diabetes in 194 non-diabetic Japanese subjects. SNP45 was associated with insulin sensitivity (determined by HOMA-IR, p=0.046) and obesity (body mass index; BMI, p=0.043). SNP276 showed a stronger association with HOMA-IR (p=0.018) and BMI (p=0.017). However, neither SNP had an association with insulin secretion (insulinogenic index) and plasma lipid levels. Moreover, a linkage dis-equilibrium was observed between SNP45 and SNP276. Carriers with SNP45G-SNP276G haplotype had higher BMI (p=0.034) and carriers with SNP45T-SNP276T haplotype had lower BMI (p=0.005) and HOMA-IR (p=0.037). Adiponectin gene variations showed an association with obesity and insulin sensitivity, and adiponectin genotypes may predict the increasing risk for type 2 diabetes in non-diabetic subjects.