The aim of this study was to evaluate the efficacy of pioglitazone (PIO) on insulin sensitivity and postprandial metabolism in patients with type 2 diabetes who were on diet control alone. Methods: This study is a randomized, doubleblind, parallel comparison study, comparing PIO 30 mg/day and placebo. A total of 27 type 2 diabetic patients (age 53.37± 0.71 years and BMI 25.77±1.78 kg/m2) who controlled their diabetes with diet alone, were randomly assigned to receive either placebo (n=14) or PIO (30 mg/day) (n=13) for 12 weeks. Before and after 12 weeks of treatment, all subjects received a modified insulin suppression test for quantitatively defining insulin sensitivity and a mixed meal tolerance test for determinations of ambient glucose, insulin and triglyceride. Results: After 12 weeks of PIO treatment, PIO resulted in a significant reduction of fasting plasma glucose (FPG) (11.03±1.11 vs 9.53±1.36 mmol/L, P<0.005), fasting plasma insulin (FPI) (197.16±22.06 vs 155.78±14.29 pmol/L, P<0.05) and HbA1c (9.20±0.36 vs 8.25±0.44%, P<0.005). There was no significant effect of PIO treatment on fasting lipid profile. The steady-state plasma glucose (SSPG) level was also significantly decreased (18.64±1.54 vs 15.67±1.66 mmol/L, P<0.05) with similar steady-state plasma insulin (SSPI) concentration. Both postprandial plasma glucose and insulin levels were ameliorated (P<0.05) without a significant effect on postprandial triglyceride concentration. Conclusions: PIO not only improves fasting glycemic index and insulin sensitivity, but also has a marked benefit on postprandial glycemic control, with a reduction of postprandial insulin levels. However, PIO could not improve postprandial triglyceride concentrations in type 2 diabetic patients.