The PGC-1 gene has been implicated in the regulation of several genes controlling energy metabolism. The prevalent Gly482Ser polymorphism of the PGC-1 gene has been shown to be associated with type 2 diabetes in some but not all studies. The aim of this study was to analyse whether the Gly482Ser variant is a risk factor for development of type 2 diabetes in Slovene population (Caucasians). Genotyping of the Gly482Ser polymorphism was performed for 545 subjects: 305 patients with type 2 diabetes and 240 non-diabetic controls. The Gly482Ser genotype distribution in patients with type 2 diabetes (AA = 11.5%, AG = 42.3%, GG = 46.2%) differed from genotype distribution in non-diabetic controls (AA = 6.3%, AG = 46.3%, GG = 47.5%), and the AA genotype was associated with 1.9-times increased risk of type 2 diabetes (95% confidence interval 1.0-3.6; P = 0.036). In conclusion, we suggest that the AA genotype of the Gly482Ser polymorphism of the PGC-1 gene should be considered as a risk factor for the development of type 2 diabetes in Caucasians.