Experimental intracerebral infection of SJL/J mice with Theiler`s murine encephalomyelitis virus (TMEV) represents an important model of chronic progressive multiple sclerosis (MS).Five-week-old female SJL/JHanHsd mice were intracerebrally infected with the BeAn-strain of TMEV. Groups of six TMEV-infected or mock-infected mice were killed 98 days post infection. Immunohistochemistry was employed to detect CD3-, CD45R/B220-, and MAC3-positve cells, as well as myelin basic protein. Microarray analysis of spinal cord RNA was performed employing Affymetrix mouse genome 430 2.0 arrays.Pathohistological examination revealed a moderate multifocal lymphohistiocytic meningo-leukomyelitis with demyelination. Sequential filtering of the microarray data resulted in a list of 923 probe sets with a changed gene expression. The pathways mainly affected were leukocyte extravasation, natural killer cell signaling as well as antigen presentation and recognition. The genes with the highest absolute change in expression included the heavy chain of IgM, chemokine ligand-13 and MHC-II antigen A, alpha. Furthermore, stock-picking revealed an oppositional expression of inflammatory and oligodendrocyte marker genes. The inflammatory cell-associated genes including lysozym and T-cell receptor β chain joining region were prominently upregulated. In contrast, myelin-associated genes such as myelin oligodendrocyte glycoprotein were mildly but significantly decreased.In summary, the presented analysis of the transcriptional changes in TME revealed that the inflammatory infiltrates in the demyelinating plaques seemed to represent the main factor influencing gene expression. Conclusively, in the late stage of TME a complex (dys)-regulation of immune- and myelin-related pathways seems to be associated with demyelination.