We investigated the metabolic effects of switching from sulfonylurea (SU) to troglitazone (TR) in 14 patients with mild (Hb A1c<7%) non-insulin-dependent diabetes mellitus (NIDDM). BMI, FPG, fasting IRI and C-peptide, Hb A1c, lipid profile, and homeostasis model insulin resistance index (HOMA-R) were evaluated immediately before, 12 and 24 weeks after switching from low dose SU to TR (400mg/day). BMI, FPG, Hb A1c and lipid profile did not change significantly. However, IRI, C-peptide, and HOMA-R significantly decreased after switching to TR (IRI, 10.0±5.4 to 6.7±2.8μU/ml; C-peptide, 2.4±1.0 to 1.9±0.7ng/ml; HOMA-R, 3.2±2.0 to 2.1±1.0). These results indicate that swithcing to TR monotherapy ameliorates insulin resistance in mild NIDDM patients on low dose SU.