Myocarditis is a clinically serious disease; however, no effective treatment has been elucidated. The P2X7 receptor is related to the pathophysiology of inflammation in many cardiovascular diseases. The P2X7 receptor antagonist is promising as an immunosuppressive treatment; however, its role in myocarditis is still to be established. To clarify the role of the P2X7 receptor, we used a murine experimental autoimmune myocarditis (EAM) model. Mice were immunized on day 0 and 7 with synthetic cardiac myosin peptide to establish EAM. The mice with induced EAM were treated with A740003, the P2X7 receptor antagonist (n = 10), or not treated (n = 11); hearts were harvested on day 21. The P2X7 receptor antagonist improved myocardial contraction of the EAM hearts via suppressed infiltration of CD4+ T cells and macrophages. Similarly, mRNA expression of interleukin 1 beta, the P2X7 receptor and NADPH oxidase 2/4 was lower in the heart of the P2X7 receptor antagonist-treated group compared to the non-treat group. The P2X7 receptor antagonist suppressed EAM development; thus, this inhibition is promising for treating clinical myocarditis.