The purpose of this study is to find out whether the -607 C/A polymorphism in IL-18 gene promoter will affect serum IL-18 concentrations and glucose metabolism in Chinese subjects. In 232 patients with impaired glucose regulation (IGR) or type 2 diabetes and 212 subjects of normal glucose regulation (NGR), -607 C/A polymorphism was analyzed by polymerase chain reaction with sequence specific primers. Serum IL-18 concentrations were determined by ELISA in 200 subjects. Compared with subjects with NGR, those with type 2 diabetes and IGR had significant higher IL-18 concentrations [114.4 (92.9-149.2) and 102.1 (67.5-138.2) vs. 77.3 (53.8-107.8) pg/ml, P = 0.0026 and P < 0.0001, respectively]. A significantly higher proportion of A/A genotype of -607 C/A polymorphism presented in patients with type 2 diabetes compared with subjects of NGR (23.8% vs. 10.9%, P = 0.005). Subjects with an A/A genotype also had higher 2 h post-loading plasma glucose (2 h-PPG) compared with C/A and C/C genotypes even after adjustments of age, sex and BMI [8.94 (7.55-12.3) vs. 7.80 (6.00-9.87) and 7.23 (5.66-8.99) mmol/l, P both < 0.05]. Multiple linear regression revealed that BMI (P < 0.0001) and 2 h-PPG (P = 0.019) were independently associated with IL-18 concentrations. In conclusion, subjects with IGR or type 2 diabetes had significantly higher concentrations of IL-18 than those with NGR. Genotype A/A of IL-18 gene promoter -607 C/A polymorphism was associated with higher prevalence of type 2 diabetes and 2 h post-loading plasma glucose level.