Previous studies have suggested that low-grade systemic inflammation is involved in the pathogenesis of type 2 diabetes mellitus. However, limited information is available about the relationship of diabetes mellitus and inflammation in Asia. We examined the association between high-sensitivity C-reactive protein (CRP) levels and diabetes in a general Iranian population. In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of men and women aged > or = 25 years, a random sample of 1754 (49.2 percent males, 50.8 percent females) subjects were evaluated. High sensitivity C-reactive protein was measured by enzyme-linked immunosorbent assay. Elevated serum CRP was defined as more than 3.0 mg/l. The diabetes classification was based on the criteria of the American Diabetes Association. A total of 8.6 percent of the subjects (8.0 percent of males & 9.1 percent of females; p>0.05) had type 2 diabetes mellitus. Geometric mean of CRP was 1.94 mg/l (3.80 SD) in the studied population. The subjects with diabetes had a higher geometric mean of CRP levels than the subjects with no diabetes [3.67 (SD 3.71) versus 1.85 (3.83) respectively; p<0.0001)]. In multiple logistic regression analysis, diabetes showed a significant age-adjusted association with elevated CRP levels [Odds Ratio = 2.03, Confidence Interval (1.38-2.98); p<0.0001] after adjusting for sex, LDL-cholesterol, HDL-cholesterol blood pressure, smoking and body mass index. In conclusion, beyond traditional cardiovascular risk factors, elevated CRP is significantly correlated with diabetes in general population of the northern Persian Gulf. Further insight into the specific effects of proinflammatory cytokines and acute-phase proteins will be essential for the development of new preventive strategies for diabetes mellitus.