Abstract In the present study, we demonstrate that the histopathologic features of myelin oligodendrocyte glycoprotein (MOG) peptide 35–55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice closely mirror the hallmarks of MS pathology. On the one hand, we depict a time-dependent transition from acute inflammation to chronic neurodegeneration in spinal cord histopathology and provide distinct criteria (i.e. parenchymal edema, cellular infiltration and perivascular inflammatory infiltrates) by which acute and chronic stages of the disease can be distinguished. On the other hand, we assessed the extent of spinal cord plaque formation in relation to the total white matter area and we demonstrate a strong correlation with the clinical disease severity. Additionally, we report on the involvement of different spinal cord regions, focusing on the anterolateral, posterior and pyramidal tract. Our results help to further characterize histopathology of MOG peptide 35–55-induced EAE and reinforce the importance of this model for structural and functional studies of MS features.