The prevalence of type 2 diabetes in the Oji-Cree of Northern Ontario is among the highest of any population in the world. We previously demonstrated that markersD8S264andD22S683were both linked and associated with type 2 diabetes in the Oji-Cree. Among the possible candidate genes for type 2 diabetes and related traits on chromosomes 8p and 22q wereNAT2andCYP2D6,respectively. We thus explored the possible association ofNAT2andCYP2D6alleles and diabetes-related traits in a sample of 112 Oji-Cree subjects with type 2 diabetes and 481 Oji-Cree subjects without type 2 diabetes. We found no difference in the allele and genotype frequencies of theNAT2G191A, C282T, C481T, G590A, A803G and G857A, and theCYP2D6G1934A polymorphisms between Oji-Cree subjects with and without type 2 diabetes. However, we found a significant association between theNAT2C282T polymorphism and plasma fasting glucose concentration. Specifically,NAT2282T/T homozygotes had significantly higher plasma fasting glucose than 282C/C homozygotes, and heterozygotes had intermediate levels of this trait. Thus, variation inNAT2orCYP2D6was not associated with the presence of type 2 diabetes, and would not be causative for this phenotype in Oji-Cree. However,NAT2might be a 'modifier gene' affecting the level of glycaemia in non-diabetic subjects.