Chronic disabilities in multiple sclerosis are believed to be due to neuron damage and degeneration, which follow remyelination failure. Due to the presence of numerous oligodendrocyte precursors inside demyelination plaques, one reason for demyelination failure could be the inability of oligodendrocyte precursor cells to turn into myelinating oligodendrocytes. In this study, we show that thyroid hormone enhances and accelerates remyelination in an experimental model of chronic demyelination, i.e., experimental allergic encephalomyelitis in congenic female Dark Agouti rats immunized with complete guinea pig spinal cord. Thyroid hormone, when administered during the acute phase of the disease, increases expression of platelet-derived growth factor alpha receptor, restores normal levels of myelin basic protein mRNA and protein, and allows an early and morphologically competent reassembly of myelin sheaths. Moreover, thyroid hormone exerts a neuroprotective effect with respect to axonal pathology.