Interleukin (IL)-13 is a cytokine produced by activated CD4+ T cells that plays a critical role in promoting allergic responses and tumor cell growth. The 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a natural ligand for the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ), a known regulator of anti-inflammatory activities. We determined the effects of 15d-PGJ2 on IL-13 expression in the Jurkat E6.1 T-cell line and in peripheral blood mononuclear cells. Semi-quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay revealed that treatment of activated T cells with 15d-PGJ2 significantly decreased IL-13 mRNA transcription and secretion, respectively. This inhibition by 15d-PGJ2 was independent of PPAR-γ since treatment with GW9662, an irreversible antagonist of the nuclear receptor, produced no effect. Our data also revealed the involvement of nuclear factor-κB in mediating 15d-PGJ2-dependent down regulation of IL-13 expression. Collectively, these results demonstrate the potential of 15d-PGJ2 in attenuating expression and production of IL-13 in activated T cells.