Introduction: It has recently been shown that polymorphisms of some genes might influence the genetic susceptibility to complex, multifactorial forms of type 2 diabetes mellitus (T2DM). One of those genes is peroxisome proliferator activated receptor γ (PPARγ). The PPARγ gene product is a nuclear hormone receptor that regulates adipogenesis and is a target for thiazolidinediones, medications enhancing sensitivity to insulin. The Pro12Ala amino acid variant of the PPARγ2 isoform is associated with T2DM in several populations. Aims: (1) To determine the allele and genotype frequency of the Pro12Ala PPARγ2 amino acid variant in a Polish population; (2) To search for the association of the Pro12Ala polymorphism with T2DM in the examined population. Methods: We included 644 individuals in this study: 366 T2DM patients with age of diagnosis greater than 35 years and 278 non-diabetic control subjects. The fragment of the PPARγ2 gene which contains the examined amino acid variant was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined based on electrophoresis of the DNA digestion products by the specific restriction enzyme BshI. Differences in distribution between the groups were examined by χ² test. Results: The frequency of Pro/Ala alleles was similar in T2DM patients and in the control subjects (83.5%/16.5% vs. 84.5%/15.5%, respectively, P=0.607). Similarly, there was no difference between the groups when we analysed the genotype distribution. Stratification analyses based on age of diagnosis, body mass index (BMI), and family history of T2DM were performed. The Pro/Ala and Ala/Ala genotypes tended to be more frequent in T2DM cases with age of diagnosis >50 years than in controls (36.2% vs. 27.3%, P=0.046). This difference was not significant after Sheffe correction for multiple comparisons. The other stratification analyses did not show any difference between the groups. Conclusion: The frequency of the Pro12Ala PPARγ2 polymorphism in the Polish population studied is similar to that in other Caucasian populations. In the case-control study, we were not able to confirm earlier reports that the Pro allele conferred an increased risk for development of T2DM. Moreover, the results of the stratified analysis suggest an opposite trend in late onset T2DM.