To test whether the beneficial effects of coffee consumption in metabolism might be explained by changes in circulating levels of adiponectin, we evaluated self-reported habitual coffee and tea consumption and caffeine intake as predictors of plasma adiponectin concentrations among 982 diabetic and 1,058 nondiabetic women without cardiovascular disease from the Nurses' Health Study. Women with and without diabetes who drank >or=4 cups of coffee per day had significantly higher adiponectin concentrations than those who didn't drink coffee regularly (7.7 vs. 6.1 microg/ml, respectively, in diabetic women, P = 0.004; 15.0 vs. 13.2 microg/ml in nondiabetic women, P = 0.04). Similar associations were observed for caffeine intake. We confirm previously reported inverse associations of coffee consumption with inflammatory markers, C-reactive protein, and tumor necrosis factor-alpha receptor II. Adjustment for adiponectin did not weaken these associations, and adjustment for inflammatory markers did not attenuate the association between coffee consumption and adiponectin concentrations. High consumption of caffeine-containing coffee is associated with higher adiponectin and lower inflammatory marker concentrations.