Multiple Sclerosis (MS) is a chronic auto-immune demyelinating and neurodegenerative disease of the CNS. It represents the leading cause of non-traumatic disability in young adults and especially women. Despite all the efforts of researchers, the exact cause of MS remains unknown to this day. According to them, MS is considered a disease that occurs in the presence of environmental factors combined with genetic factors. Current therapy uses drugs that suppress immunological attacks without suppressing the entire immune system. Melatonin has been shown to be a potent neuroprotective candidate to reduce the loss of myelin.The aim of this work is to examine the clinical correlation between serum melatonin and proCT in MS patients and to assess the effect of melatonin on osteoporosis, metabolic pathways and remyelination in the brain. in vivo. To do this, different molecular and cellular biology techniques were used in the experimental model of autoimmune encephalomyelitis (EAE).The results obtained are divided into three parts. In the first part, the data showed a significant increase in serum proCT levels in MS patients, inversely correlated with melatonin and osteocalcin OCN levels compared to healthy subjects. In the second part, we demonstrated that melatonin decreased the average clinical scores, significantly reduced serum proCT levels and increased the level of 25-hydroxyvitamin D, calcium and OCN in EAE mice compared to control EAE mice. In the third part, the results showed that melatonin increased the level of anti-inflammatory cytokines (interleukin-10 (IL-10) and interleukin-4 (IL-4)) and decreased the rate of pro-inflammatory cytokines (tumor necrosis factor – alpha (TNF-α) and interleukin 1-beta (IL-1β)) in EAE mice compared to control EAE mice. We also demonstrated that the level of myelin oligodendrocyte glycoprotein (MOG), the level of myelin basic protein (MBP) and the level of myelin oligodendrocytic basic protein (MOBP) wereincreased by it. In addition, it has led to a significant increase in brain concentrations of acetate, N-acetylaspartate (NAA) and 3-hydroxy-3-methylglutaryl-Coenzyme-A reductase (HMGCR). Expression levels of mRNA and pyruvate dehydrogenase kinase-4 (PDK-4) proteins also increased in melatonin-treated mice compared to untreated EAE mice. Treatment with melatonin resulted in increased lactate levels in the brain, while the activity of the active and total pyruvate dehydrogenase (PDC) complex, an enzyme under the control of PDK-4, was suppressed.In conclusion, this study suggests that ProCT may be a biomarker in patients with MS. The results obtained on melatonin-treated EAE mice demonstrate its importance in reducing the severity of the disease and intracerebral inflammation, as well as improving bone metabolism, which consequently reduces osteoporosis. Likewise, this treatment is important for the reduction of inflammatory mediators while stimulating oligodendrogenesis. Thus, melatonin exerts a modulatory effect on the metabolic pathways involved in brain metabolism and improves mitochondrial dysfunction.