Objective: To find out the relation between Pro 12 Ala polymorphism of peroxisome proliferator- activated receptor gamma2 (PPAR-g2) gene with type 2 diabetes mellitus and the possible role of this gene polymorphism as a link between obesity and type 2 diabetes mellitus. Subjects and Methods: Subjects of this study were classified into 3 groups: (15) Apparently healthy lean individuals (Group I), (15) obese non diabetic individuals (group II) and (24) patients with type 2 diabetes mellitus (group III). This group divided into: Diabetic non obese patients (12 patients) (Group IIIa) and: Diabetic obese patients (12 patients) (Group IIIb). The subjects were subjected to clinical examination, serum insulin level and estimation of PPAR-g2 gene polymorphism by Restriction fragment length polymorphism (RFLP) polymerase chain reaction (PCR). Results: Frequency of Pro allele was significant increase in diabetic non obese patients& diabetic non obese patients when compared to control group (P= 0.048 and 0.003, respectively). However, there was no difference between obese non diabetic group and control group as regard the allelic frequencies (p= 0.462). While diabetic non obese patients had higher Pro allele frequency (p= 0.003) than in diabetic obese patients (p= 0.048). Insulin resistance by homeostasis model assessment (HOMA-IR) was significantly increased in Pro/Pro carriers in group II and group III when compared to that of Pro/Ala plus Ala/Ala carriers (p= 0.004 and 0.023; respectively). Conclusion: Pro12 allele of PPAR-g2 gene could be a genetic risk factor for insulin resistance and type 2 diabetes mellitus.