To investigate whether gene polymorphisms of both adiponectin and peroxisome proliferator-activated receptor gamma (PPARγ) influence type 2 diabetes mellitus (T2DM) respectively in the Han people of the Wenzhou region of China and whether the interaction of gene polymorphism between adiponectin and PPARγ influences T2DM in the same subjects.This study included 198 patients with T2DM and 255 healthy individuals. Polymerase chain reaction-restriction fragment length polymorphism analyses were used to detect single nucleotide polymorphisms (SNPs). Logistic regression and multifactor dimensionality reduction (MDR) methods were used to analyze gene-gene interactions.The frequency distribution of adiponectin SNP11377 was not different (p=0.792), but the frequency of CC, CG and GG genotypes showed the difference between two groups (T2DM: 57.1%, 33.3%, and 9.6%; control: 53.7%, 41.6%, and 4.7%, respectively; p=0.047). Adiponectin SNP45, SNP276 and PPAR γ SNPp12a were equally distributed between the two groups (p=0.586, 0.119, 0.437, respectively), and there were no significant differences in genotype frequencies between the two groups (p=0.751, 0.144, 0.479, respectively). Linkage disequilibrium existed between SNP11377 and SNP45 (p<0.001) and SNP45 and SNP276 (p<0.001). Haplotype analyses showed no significant differences between the T2DM and control groups. According to the logistic regression and MDR gene-gene interaction analyses, SNP11377GG and SNP276GT interactions increased the risk of T2DM (odds ratio=6.984, p=0.012).Adiponectin SNP11377 and SNP276 gene-gene interactions are associated with the increased risk of T2DM in this population.