Peroxisome proliferator-activated receptor gamma2 (PPARgamma2) is a nuclear receptor that regulates adipocyte differentiation, lipid metabolism, and insulin sensitivity. The aim of this study was to investigate the association between the Pro12Ala single nucleotide polymorphism (SNP) at the PPARgamma2 gene and type II diabetes (T2DM) and obesity in an Iranian population.The genomic DNA of the 312 subjects included four groups: (1) nonobese with type II diabetes, (2) obese without type II diabetes, (3) obese with type II diabetes, and (4) nondiabetic nonobese controls. The Pro12Ala polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.Frequencies of the Ala allele in obese subjects were significantly different from those control subjects (odds ratio [OR], 2.358; 95% confidence interval [CI], 1.101-5.05) (P = 0.025). In contrast, no significant association was detected between the Pro12Ala polymorphism and type II diabetes (OR, 0.652; 95% CI, 0.261-1.628). In all subjects, the Ala carriers had a higher body mass index (BMI) compared with the common allele.Our results showed that the Pro12Ala polymorphism in the PPARgamma2 gene is associated with obesity in Iranian subjects and the presence of the Ala allele could predict higher BMI.