Erythropoietin (EPO) has been known to have cytoprotective effects on several types of tissues, presumably through modulation of apoptosis and inflammation. The effect of EPO on myocardial inflammation, however, has not yet been clarified. We investigated the cardioprective effects of EPO in rats with experimental autoimmune myocarditis (EAM). Seven-week-old Lewis rats immunized with cardiac myosin were treated either with EPO or vehicle and were examined on day 22. EPO attenuated the functional and histological severity of EAM along with suppression of mRNAs of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in the hearts as well as a reduction of apoptotic cardiomyocytes. The EPO receptor (EPO-R) was upregulated in the myocardium of EAM compared with that of healthy rats. These results may suggest that EPO ameliorated the progression of EAM by modulating myocardial inflammation and apoptosis. (c) 2006 Elsevier Inc. All rights reserved.