Background/Aims: Recent evidence shows that peroxisome proliferator-activated receptor-γ (PPAR-γ) ameliorates a variety of inflammatory conditions. CD40 is a co-stimulatory molecule and its ligation induces production of different proinflammatory cytokines including RANTES (regulated upon activation, normal T cell expressed), which are considered as important factors in the initiation and maintenance of inflammatory response. The aim of this study was to investigate the effect of PPAR-γ on CD40 and RANTES production on cultured human renal proximal tubular epithelial (HK-2) cells. Methods: HK-2 cells were maintained under defined in vitro conditions and treated with either PPAR-γ agonist 15-deoxy-12,14-prostaglandin J<sub>2</sub> (15d-PGJ<sub>2</sub>) or 15d-PGJ<sub>2</sub> + PPAR-γ antagonist GW9662, and then stimulated with a combination of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The CD40 and RANTES levels were investigated. Results: HK-2 cells expressed low levels of CD40 and RANTES. Activation of HK-2 cells by combined treatment of TNF-α and IFN-γ results in strong synergistic effects on the expression of CD40 and the secretion of RANTES. 15d-PGJ<sub>2</sub> significantly decreased CD40 and RANTES expression and GW9662 partly abrogated the inhibition of 15d-PGJ<sub>2</sub> on CD40 and RANTES. Conclusion: 15d-PGJ<sub>2</sub> significantly decreased CD40 and RANTES expression in HK-2 cells, which were partially mediated by PPAR-γ-dependent pathways. These results point to PPAR-γ as a remarkable new target in the prevention of tubular inflammatory injury associated with renal disease.