Myelin producing human oligodendrocytes express the main thyroid hormone plasma membrane transporter, monocarboxylate transporter 8 (MCT8). Our group has demonstrated that MCT8 is dysfunctional in conditions of developmental or acquired myelin diseases such as progressive multiple (MS). Small molecules that can bypass MCT8, such as the thyroid hormone analog, diiodothyropropionic acid (DITPA), may improve re-myelination and provide neuroprotection in the central nervous system (CNS), following immune-mediated damage described in a mouse model that mimics MS-like disease.Using the myelin oligodendrocyte glycoprotein peptide (MOG)-induced mouse model of neuroinflammation, experimental autoimmune encephalomyelitis (EAE), and thorough proteomic analyses, our group has described dysregulation in key phosphorylated proteins associated with thyroid hormone-dependent signaling during acute inflammatory spinal cord demyelination and axonal damage in the peak-stage of EAE. By benchmarking thyroid hormone analogs in a preclinical randomized controlled study, we identified that the daily administration of DITPA at 1.5 mg/kg body weight can promote neurological recovery of EAE-induced mice from disease onset. Furthermore, we identified enhanced re-myelination in the optic nerves of EAE-induced mice treated with DITPA by investigating the ultrastructure of nerve fibres around axons using transmission electron microscopy and a comprehensive analysis of myelin thickness (G-ratio), size, distribution and integrity.Collectively, our data suggest the importance of MCT8 in oligodendrocyte survival, maturation, and differentiation in the CNS during neuroinflammation and that DITPA is a promising therapeutic for CNS inflammatory damage to promote neuroprotection and repair.