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To test the hypothesis that rosiglitazone combined with metformin provides a greater reduction in microalbuminuria and blood pressure than metformin and glyburide at comparable levels of glycemic control.In a double-blind, parallel-group design 389 participants with type 2 diabetes were followed for 32 weeks.Urinary albumin: creatinine ratio was significantly reduced at 32 weeks compared with baseline in the rosiglitazone plus metformin group (−22.7%; P < 0.01) but not in the glyburide plus metformin comparator group (−7.1%; P = 0.32). Patients who completed the study (81.5%) demonstrated a treatment difference of −19.5% (P = 0.03), favoring the rosiglitazone group. Rosiglitazone plus metformin reduced both mean 24-h systolic (−3.4 mmHg; P = 0.01) and diastolic (−2.5 mmHg; P < 0.01) ambulatory blood pressure compared with glyburide plus metformin. Addition of rosiglitazone to metformin also reduced levels of plasminogen activator inhibitor-1 antigen and activity, C-reactive protein, von Willebrand factor and fibrinogen compared with addition of glyburide.Rosiglitazone added to background therapy with metformin provides greater reductions in microalbuminuria and blood pressure as compared with glyburide. These additional improvements in microalbuminuria, blood pressure and cardiovascular biomarkers were observed despite comparable improvements in glycemic control in both groups and may be related to the anti-inflammatory properties of rosiglitazone.