Plasma levels of adiponectin are lower in obese and insulin-resistant subjects compared with lean and insulin-sensitive ones. Thiazolidinediones increase plasma adiponectin levels in diabetic subjects, although the mechanism of this increased plasma adiponectin has not been well studied. In the present study, we compared the plasma levels and adipose tissue expression of adiponectin in subjects with normal (NGT) and impaired glucose tolerance (IGT) and also studied the effects of metformin and pioglitazone on plasma and adipose tissue mRNA level of adiponectin in IGT subjects. IGT subjects had lower plasma adiponectin levels compared with NGT subjects, and similarly IGT subjects had lower adiponectin mRNA levels. In contrast, the increased plasma levels of adiponectin in response to pioglitazone were not associated with increased adiponectin expression in adipose tissue. Metformin did not cause any change in plasma or expression levels of adiponectin. Other adipokines were examined, and both pioglitazone and metformin decreased plasma levels of resistin in IGT subjects, and pioglitazone (but not metformin) decreased plasma levels of leptin. These data suggest that pioglitazone increases plasma adiponectin levels by posttranscriptional regulation in contrast to transcriptional regulation of adiponectin in relation to insulin sensitivity in NGT vs. IGT subjects.