Prostaglandins (PG) and their specific receptors for E type PG (EP) play an important role in inflammatory diseases. Although myocarditis results in inflammation of the heart, roles of PG and EP in its pathophysiology is still controversial. To clarify the role of PG and EP on the progression of myocarditis, we used an experimental autoimmune myocarditis model. A selective EP4 (EP4RAG) agonist was administered into both early (Day 0 to 21) and late (Day 14 to 21) -treated groups and the animals were killed on Day 21. We found that improved cardiac function was detected in the EP4RAG-treated groups in comparison to the untreated group. The infiltration area ratio in the early-treated (16.6% ± 4.6%) group was lower than those in the untreated group (32.1% ± 3.5%) (P < 0.05). The fibrosis area ratios in the early-treated (19.2% ± 6.3%) and the late-treated groups (24.4% ± 5.1%) were lower than those in the untreated group (37.4% ± 2.6%), respectively (P < 0.05). Moreover, we found that EP4RAG decreased T-cell proliferation and monocyte chemoattractant protein-1 production in vitro. We concluded that a selective EP4 agonist inactivates T-cells, which turns out to moderate the progression of experimental autoimmune myocarditis. Therefore, EP4 can be an effective target for myocarditis treatment.