The precise mechanism by which PPAR gamma activation by thiazolidinediones (TZDs) improves insulin sensitivity is still unclear. Recent studies have focused on the role of adipocytokines, in metabolic control and their regulation by TZDs. In this study, we compared the chronic effects of antihyperglycemic doses of the TZD rosiglitazone, the beta3-adrenoceptor agonist BRL-35135, and the PPAR alpha agonist Wy-14,643 on the m-RNA expression of adipocytokines in WAT of db/db mice. Rosiglitazone treatment decreased adiponectin and resistin mRNA levels by 57 and 72%, respectively (P<0.001), with no effect on the level of TNF or RELM alpha transcripts. In comparison, Wy-14,643 reduced adiponectin transcript levels by 31% (P=0.015) while BRL-35135 increased RELM alpha mRNA expression by 245% (P<0.001) without effect on the other transcripts. Our results indicate that although a reduction in adiponectin and resistin mRNA levels in WAT by rosiglitazone treatment of diabetic mice may contribute to the antidiabetic effects, an alteration in TNF, adiponectin, resistin, or RELMa mRNA expression is not absolutely required for the regulation of blood glucose concentration in the db/db mouse.