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Whether free fatty acid (FFA) rate of appearance (R_a) is increased in type 2 diabetes is controversial. To characterize nocturnal and postprandial abnormalities in FFA kinetics and to determine the effects of treatment with insulin sensitizers on lipolysis, we measured palmitate R_a in control subjects (n = 6) and individuals with poorly controlled, sulfonylurea-treated type 2 diabetes (HbA_1c = 8.7 ± 0.2%, n = 20), the latter before and at the end of 12 weeks of treatment with troglitazone (600 mg/day, n = 4), metformin (∼2,000 mg/day, n = 8), or placebo (n = 8). Subjects consumed a standard breakfast at 0800 h. Results in control subjects and type 2 diabetic subjects were compared at baseline. Integrated nocturnal FFA R_a (AUC_{1:00–8:00 a.m.}) was ∼50% higher in type 2 diabetic subjects than in control subjects (29.4 ± 3.0 vs. 19.4 ± 3.9 mmol · m⁻² · 7 h⁻¹, respectively, P < 0.05), whereas postprandial palmitate R_a (AUC …