OBJECTIVES: Multiple sclerosis is a chronic infl ammatory and autoimmune demyelinating disease of the brain and spinal cord. Vitamin D has anti-infl ammatory and anti-Th1, Th17 activities, activates the function of regulatory T cells, shifts the immune response towards Th2, so it might be favorable for downregulation of the disease pathogenesis, and if infl ammation and Th1 and Th17 immunity are hyperactivated. The aim of our study was to highlight the role of vitamin D in multiple sclerosis pathogenesis. METHODS: We investigated 178 patients with multiple sclerosis. Plasma levels of 25(OH)D and HMGB1 were investigated. RESULTS: Despite a regular use of VD by patients, the plasma levels of 25(0H)D were signifi cantly decreased in 57% of them, 14.1% had VD defi ciency (level of 25(OH)D < 20 ng/mL) and more than 6 % of patients had VD severe defi ciency with the plasma level of 25(OH)D < 12 ng/mL. The level of 25(OH)D negatively correlated with the severity of the disease (EDSS, index of progression, duration of the disease) and negative association was found also with Herbert´s six severity grades. HMGB1 levels were higher in patients (p < 0.0001). CONCLUSION: Our result showed that vitamin D defi ciency plays a role in multiple sclerosis pathogenesis. We believe that administration of vitamin D to patients at a suffi cient dose providing a physiological level of vitamin D could have a positive effect on the course of the disease. However, regular monitoring of vitamin D levels is required, which should be at least within 30-75 ng/mL, and even more, but below the toxicity limit