Abstract Aims The aim of this study was to investigate the association of four single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptor gamma (PPARG) with type 2 diabetes mellitus (T2DM) risk and additional role of gene-obesity interaction. Methods Four SNPs were selected for genotyping in the case–control study: rs1805192, rs709158, rs3856806 and rs4684847. Generalized multifactor dimensionality reduction (GMDR) model and logistic regression was used to examine the interaction between SNP and obesity on T2DM, odds ratio (OR) and 95% confident interval (95% CI) were calculated. Results T2DM risk was significantly higher in individuals with rs1805192-G allele ( p