Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS).  Unlike other demyelinating mouse models, cuprizone autoimmune encephalitis (CAE) has the potential to recapitulate key elements of the MS lesion environment specifically within the brain.  To examine this possibility, mice received 2 weeks of cuprizone (0.2% w/w) in standard chow to biochemically alter brain myelin, after which they receive complete Freund’s adjuvant and Pertussis toxin to activate the peripheral immune system.  Brain tissue was collected 21 days later.  By performing immunohistochemistry, we determined within the CAE brain there was CD3⁺ T cell infiltration of the corpus callosum (p=0.0001), and reduced myelin basic protein (MBP) expression (p=0.0001). This demyelination was associated with decreased oligodendrocyte densities (p=0.0001). We also detected evidence of gliosis, including microgliosis (p=0.01), astrogliosis (p=0.0001) and an increase in oligodendrocyte progenitor cell densities (p=0.01).  To examine if these OPCs can differentiate into new premyelinating or myelinating oligodendrocytes within the CAE lesion environment, we have fluorescently labelled and fate mapped OPCs in young adult Pdgfra-CreER^TM :: Rosa26-YFP transgenic control and CAE mice.  We hypothesise that new oligodendrocyte survival will be significantly impaired within CAE lesions.  We conclude that the CAE model of inflammatory demyelination recapitulates key elements of MS pathophysiology, providing insight into how the this condition may affect key cells within the CNS.