Type 2 diabetes is a major risk factor for myocardial infarction (MI) and chronic inflammation may play a central role in both diseases. Interleukin (IL)-18 is a potent proinflammatory cytokine, which is considered important in acute coronary syndromes and type 2 diabetes. We investigated the association of the -137 (G>C), polymorphism (rs187238) and the -607 (C<A) polymorphism (rs1946518) of the IL-18 gene promoter region in 495 Caucasians with type 2 diabetes, of whom 169 had MI and 326 subjects had no clinically evident coronary artery disease (controls). We also investigated the impact of these polymorphisms on the serum IL-18 level in subsets of both groups and in a normal group. Genotype distributions of the polymorphisms showed no significant difference between cases and controls. However, IL-18 serum levels were significantly lower in diabetics with the137 CC genotype than in those with other genotypes (241.5 ± 132.7 ng/L