OBJECTIVE: Increasing evidence from a cohort of Caucasians recently suggests that an elevated level of C-reactive protein (CRP) is associated with an increased risk of developing type 2 diabetes. However, Japanese subjects are skewed to lower CRP concentrations than westerners. Therefore, the effect of CRP on the development of type 2 diabetes among Japanese is unclear. RESEARCH DESIGN AND METHODS: We examined 396 male and 551 female nondiabetic Japanese Americans who underwent a 75-g oral glucose tolerance test (GTT) and were then followed for an average of 6.5 years. We investigated whether elevated serum CRP level is a risk factor in the development of type 2 diabetes among these subjects. RESULTS: Subjects with a high CRP level showed a significantly higher incidence of type 2 diabetes compared with subjects with a low level among both men (P = 0.028) and women (P = 0.004) in a log-rank test. In a Cox proportional hazards model dividing quartiles of CRP, the hazard ratios for diabetes development in the highest versus lowest quartile of CRP levels were 2.84 (95% CI 1.09-7.39) among men and 3.11 (1.25-7.75) among women after adjustment for age, smoking, family history of diabetes, classification of a 75-g GTT, hormone replacement therapy (among women), BMI, and homeostasis model assessment. CONCLUSIONS: Among Japanese Americans, CRP may be a risk factor for development of type 2 diabetes independent of either obesity or insulin resistance. Our results suggest that inflammation may be closely related to the mechanism of type 2 diabetes among Japanese Americans.