Some angiotensin II receptor type 1 antagonists are reported to inhibit proinflammatory cytokine production in vitro and in vivo. However, the effects of the drugs upon autoimmune diseases are unknown. We tested the hypothesis that olmesartan, a novel angiotensin II receptor type 1 antagonist, ameliorated experimental autoimmune myocarditis (EAM) in rats attributing to the suppression of inflammatory cytokines as well as to the immunomodulating action for the heart. We orally administered olmesartan 1mg/kg/day, 3mg/kg/day, and 10mg/kg/day to rats with EAM for 3 weeks. The results showed that olmesartan decreased blood pressure significantly compared with the untreated group, and markedly reduced the severity of myocarditis associated with the decrease of myocardial macrophage, CD4+, and CD8+ T cell expression by comparing the heart weight/body weight ratio, pericardial effusion scores, macroscopic and microscopic scores. Myocardial interleukin-1 (IL-1)-positive staining cells by immunohistochemistry and IL-1 expression by western blotting were significantly lower in rats with EAM given olmesartan treatment compared with those of rats given vehicle. Cardiac myosin-specific delayed type hypersensitivity was significantly lower in olmesartan-treated rats than in control rats. The cytotoxic activities of lymphocytes in rats with EAM treated with olmesartan were reduced compared with untreated controls. In vitro study showed that both olmesartan and its active metabolite, RNH-6270, suppressed IL-1 production in U937 cells and cultured myocytes. Olmesartan ameliorates acute EAM in rats. The cardioprotection of olmesartan may be due to suppression of inflammatory cytokines as well as to suppressive effects for cytotoxic myocardial injury in addition to the hemodynamic modifications.