Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, and in this study we used quantitative proteomics to compare the brain proteomes of two MS mouse models, the immune-mediated experimental autoimmune encephalomyelitis (acute and recovery phase) and cuprizone (late de-/remyelination) with that of corresponding control mice. Proteomics using LC-MS with TMT-labeling and label-free quantification resulted in the quantification of 3664 and 2582 proteins (including protein groups), respectively, a total of 4375 different proteins. Differences between the disease model mice and the controls were revealed and protein candidates were discovered and translated to human disease.