Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily. They regulate lipid metabolism, glucose homeostasis, cell proliferation, and differentiation and modulate inflammatory responses. We examined whether PPARγ is functional in cultured neonatal ventricular myocytes and studied its role in inflammation. Western blots revealed PPARγ in myocytes. When myocytes were transfected with a PPAR response element reporter plasmid (PPRE-TK-luciferase), the PPARγ activator 15-deoxy-Δ 12,14 -prostaglandin J 2 (15dPGJ 2 ) increased promoter activity, whereas cotransfection of a dominant negative PPARγ inhibited it. To determine the role of 15dPGJ 2 in expression of proinflammatory genes, we tested its effect on interleukin-1β induction of cyclooxygenase-2 (COX-2). 15dPGJ 2 decreased interleukin-1β stimulation of COX-2 by 40% and PGE 2 production by 73%. We next questioned whether 15dPGJ 2 was modulating the expression of inducible prostaglandin E 2 synthase (PGES) and found that it completely blocked interleukin-1β induction of PGES. Use of a second PPARγ agonist, troglitazone, and the selective PPARγ antagonist GW9662 demonstrated that the effects seen were PPARγ-dependent. In addition, we found that 15dPGJ 2 blocked interleukin-1β stimulation of inducible nitric oxide synthase (iNOS). We concluded that 15dPGJ 2 may play an anti-inflammatory role in a PPARγ-dependent manner, decreasing COX-2, PGES, and PGE 2 production, as well as iNOS expression.