PPAR-gamma is known to have a growth-suppressive effect in different cancers. In this study, we investigated the role of PPAR-gamma in the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EA). We used immunohistochemistry and real-time PCR to analyze differences in PPAR-gamma protein and mRNA expression levels in samples of normal esophageal squamous epithelium (n = 75), BE (n = 50), and EA (n = 25). Immunoreactivity with antibodies against PPAR-gamma was confined to the nuclei of goblet cells and surface glandular epithelium in BE samples. We found significantly lower levels of expression of PPAR-gamma protein (p < 0.01) in normal esophageal squamous epithelium when compared to BE and EA samples. PPAR-gamma protein levels showed an increasing trend from normal esophageal squamous epithelium < BE samples < EA samples (p < 0.01). PPAR-gamma mRNA expression levels in BE and EA samples were 5.9130-fold (p < 0.01) and 2.0314-fold (p < 0.01) higher than that of normal esophageal squamous epithelium, respectively. There was a trend towards increased expression of PPAR-gamma with decreasing levels of differentiation. Increased PPAR-gamma expression may play an important role in the development and progression from normal cells to BE and EA.