BACKGROUND: Plasma adipokine concentrations are variably related to fatness/insulin resistance and may act via endocrine mechanisms. We assessed the relationship among plasma adipokine concentrations and their relationship with insulin sensitivity and body composition in obese adults before and after insulin sensitization accomplished using diet/exercise or pioglitazone. METHODS: Plasma adipokine concentrations, insulin sensitivity, and body composition were assessed in 39 upper-body obese insulin-resistant, nondiabetic adults before and after 19 wk of diet/exercise or 30 mg/d pioglitazone. RESULTS: Diet/exercise reduced body fat and visceral fat and improved insulin sensitivity parameters; pioglitazone improved insulin sensitivity to a similar degree but increased body fat. Adiponectin increased more after pioglitazone (4770 +/- 487 vs. 8351 +/- 693.6 ng/ml, P < 0.001) than after diet/exercise (4704 +/- 367 to 5426 +/- 325.3 ng/ml, P < 0.01), whereas TNFalpha, IL-6, and resistin did not change. C-reactive protein decreased with diet/exercise. Adipokine concentrations were not correlated with each other at baseline or after insulin sensitization, except TNFalpha and IL-6 (r = 0.43, P < 0.05); IL-6 was inversely correlated with resistin. Only adiponectin was correlated (P < 0.05) with indices of insulin sensitivity. Adiponectin concentrations were inversely correlated with visceral fat and with sc fat depots in men but positively correlated with sc fat in women. CONCLUSION: Plasma adipokine concentrations were not consistently interrelated, and only adiponectin displayed the expected relationship with insulin sensitivity and sensitization. These findings do not support an endocrine role for resistin, TNFalpha, and IL-6 in mediating changes in insulin resistance after diet/exercise or pioglitazone.