Clinical and epidemiological data indicate that inflammation may be associated with insulin resistance. We examined the association between inflammatory markers, such as ferritin, uric acid, white cell counts, fibrinogen, and C-reactive protein, and insulin resistance among 5,959 adults, aged > or =20 years and without diabetes (fasting glucose <126 mg/dl and not taking diabetes medication), who participated in the Third National Health and Nutrition Examination Survey. Insulin resistance was calculated using the homeostasis model assessment (HOMA). Levels of ferritin, uric acid, white cell counts, fibrinogen, and C-reactive protein were significantly higher in individuals with a higher HOMA of insulin resistance (HOMA-IR). After adjustment for age, sex, race, education, physical inactivity, current and former smoking, alcohol intake, use of nonsteroidal anti-inflammatory drugs, systolic blood pressure, BMI, waist circumference, serum total cholesterol, and triglycerides, a 1-SD higher ferritin (126.1 ng/ml), uric acid (1.4 mg/dl), white blood cell count (2.2 x 10(9)/l), and fibrinogen (80.6 mg/dl) was associated with a 0.10 (95% CI 0.03-0.17, P=0.004), 0.16 (0.08-0.24, P <0.001), 0.16 (0.09-0.22, P <0.001), and 0.12 (0.05-0.18, P=0.001) higher HOMA-IR, respectively. Clinically elevated C-reactive protein (> or =1.0 mg/dl) was associated with a 0.63 (0.23-1.04, P=0.003) higher HOMA-IR. These findings indicate that elevated levels of inflammatory markers are positively and independently associated with insulin resistance. Further studies should examine the potential causal effect of inflammation on insulin resistance.