Whether the contribution of inflammation to risk for chronic metabolic disease differs with ethnicity is not known. The objective of this study was to determine: (i) whether ethnic differences exist in markers of inflammation and (ii) whether lower insulin sensitivity among African Americans vs. whites is due to greater inflammatory status. Subjects were African-American (n = 108) and white (n = 105) women, BMI 27-30 kg/m 2. Insulin sensitivity was assessed with intravenous glucose tolerance test and minimal modeling; fat distribution with computed tomography; body composition with dual-energy X-ray absorptiometry; markers of inflammation (tumor necrosis factor (TNF)-α, soluble tumor necrosis factor receptor (sTNFR)-1, sTNFR-2, C-reactive protein (CRP), and interleukin (IL)-6) with enzyme-linked immunosorbent assay (ELISA). Whites had greater intra-abdominal adipose tissue (IAAT), insulin sensitivity, and concentrations of TNF-α, sTNFR-1, and sTNFR-2 than African Americans. Greater TNF-α in whites vs. African Americans was attributed to greater IAAT in whites. Among whites, but not African Americans, CRP was independently and inversely associated with insulin sensitivity, after adjusting for IAAT (r = 0.29 P < 0.05, and r = 0.13 P = 0.53, respectively). Insulin sensitivity remained lower in African Americans after adjusting for CRP (P < 0.001). In conclusion, greater IAAT among whites may be associated with greater inflammation. Insulin sensitivity was lower among African Americans, independent of obesity, fat distribution, and inflammation. © 2008 The Obesity Society.