Objective: Recent evidence has suggested that peroxisome proliferator-activated receptor-(PPAR- ) serves as a negative regulator in the immune system. In the present study, we investigated the expression of PPAR-and the effect of PPAR-ligands on experimental autoimmune myocarditis (EAM).Methods and Results: Experimental autoimmune myocarditis was induced in Lewis rats by immunization with porcine cardiac myosin. PPAR-γ ligands 15-deoxy- 12,14-PGJ2 200μg·kg−1·d−1 by ip and pioglitazone 10mg·kg−1·d−1 by oral were administered for 3 weeks. PPAR-γexpression was upregulated in myocarditis and the enhanced PPAR-γ expression was prominently stained in the nuclear and perinuclear regions of the positive-stained cells in the inflammatory lesions. Administration of PPAR-γ ligands markedly reduced the severity of myocarditis, as indicated by the heart weight/body weight ratio, pericardial effusion scores, macroscopic scores, and microscopic scores. The upregulated PPAR- expression was also reduced by PPAR-γ ligands treatment. In addition, PPAR-ligands suppressed the proliferative response and interferon-production of T cell-enriched splenocytes from rats with EAM. Furthermore, the cytotoxic activity and myocarditogenic potential of these T cells were inhibited by PPAR-γ ligands treatment. Conclusions: PPAR-γ ligands ameliorate EAM associated with inhibition of expansion and activation of the self-sensitive T cells. These results suggest that PPAR-ligands may have the potential to modulate human inflammatory heart diseases as myocarditis.