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Background To investigate short-term effects of pioglitazone and voglibose on serum concentrations of both total and high-molecular-weight (HMW) adiponectin measured with a novel sandwich enzyme-linked immunosorbent assay (ELISA) ,and on plasma fibrinolysis indicators, in Type 2 diabetic patients with inadequate glycaemic control on sulphonylureas. Methods Thirty-four diabetic patients were randomized to receive pioglitazone or voglibose treatment for 12 weeks, after which serum HMW adiponectin was measured. Plasma plasminogen activator inhibitor (PAI) 1 and thrombin-activatable fibrinolysis inhibitor (TAFI), a recently identified inhibitor of fibrinolysis, were measured as fibrinolysis inhibitors. Results At baseline, serum HMW adiponectin correlated negatively with plasma TAFI in all patients with Type 2 diabetes ( r = –0.367, P = 0.0423). Both groups showed similar improvements in glycaemic control. Serum total and HMW adiponectin increased in patients treated with pioglitazone, but did not change in patients treated with voglibose. The HMW : total adiponectin ratio increased significantly after treatment with pioglitazone ( P = 0.0004). The change in HbA1c correlated negatively with changes in serum HMW adiponectin in patients treated with pioglitazone ( r = –0.694, P = 0.0034). Plasma PAI-1 and TAFI did not change with pioglitazone treatment. Conclusion Increased serum HMW adiponectin may contribute to the improvement in glycaemic control after pioglitazone treatment. Plasma PAI-1 and TAFI were unchanged by either drug. [ABSTRACT FROM AUTHOR]