Peroxisome proliferator-activated receptor-gamma (PPARgamma) may play a protective role in the regulation of vascular function, partly mediated by its effects on superoxide dismutase (SOD). The aim of this study was to determine the association between PPARgamma expression in peripheral blood mononuclear cells (PBMCs) and SOD activity in morbidly obese persons with varying degrees of insulin resistance (IR). We studied in 10 morbidly obese persons (five with no IR and five with high IR) the effect of a high-fat meal on the plasma activity of various antioxidant enzymes and the mRNA expression of PPARgamma in PBMC. The high-fat meal resulted in a significant decrease in plasma SOD activity, glutathione reductase (GSH-Rd) activity, and mRNA expression of PPARgamma only in the group of morbidly obese persons with high IR. PPARgamma expression after the high-fat meal correlated with the IR levels (r = -0.803, P = 0.009) and the plasma SOD activity (r = 0.903, P = 0.001). Likewise, the reduction in PPARgamma expression correlated with the increase in free fatty acids (FFA) (r = 0.733, P = 0.016). In conclusion, the decreased expression of PPARgamma in PBMC in morbidly obese persons after a high-fat meal was associated with the state of IR, the plasma SOD activity, and the changes in the concentration of FFA.