BACKGROUND Rheumatoid myositis (RM) represents a poorly characterized entity, immune mechanism, assessment and management remaining still unclear. The aim of this study was to investigate endothelial and inflammatory cells activation in RM muscle biopsy. METHODS Prospective study on 23 consecutive rheumatoid arthritis (RA) with muscle involvement as defined by clinical, biological and imagistic parameters. CD4, CD8, CD20, CD3, CD45RO and CD68 markers, HLA-DR, cytokines receptors (IL-2, TNFalpha, TGF alpha), pro-apoptotic (CD95) and adhesion molecules (CD54) were assessed by immunohistochemistry in deltoid muscle samples. RESULTS (1) endomysial, perivascular and perimysial inflammatory infiltrates and moderate muscle fibers involvement; predominance of activated (HLA-DR+), memory (CD45RO+) CD3+TCD8+ cells and macrophages surrounding and invading non-necrotic muscle fibers (34.78%) and TCD4+ activated cells in perivascular and perifascicular areas (65.22%); (2) up-regulation of HLA-DR, CD54 and IL-2R on both endothelial cells and lymphocytes (85%); (3) aberrant increased CD95 in endothelial cells without any other apoptotic sign (83%) have been described. CONCLUSIONS Increased expression of activation markers, adhesion molecules and cytokine receptors may indicate early endothelial activation in RM pathogenesis, while endomysial TCD8+ activation may account for further development and perpetuation of myositis.