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Background and Objectives: The prevalence of multiple sclerosis (MS) differs between different regions of Iran. This study aimed to investigate changes in prevalence and incidence rates of MS in ten ethnic and cultural zones of Iran set by the Ministry of Health and Medical Education. Materials and Methods: Information on MS incidence and prevalence was obtained from the national registry of MS during the study period 2006–2013. Demographic data were acquired from the Statistical Centre of Iran. Results: A rising trend of MS prevalence was observed in Iran, and overall, the prevalence of MS increased by 3.67% per year. The highest prevalence rates of MS, and the most dramatic increase in MS prevalence, occurred in the central areas of Iran. However, during the 7-year period, the prevalence gradually increased also in southern and western areas. Conclusion: The prevalence and incidence of MS have been rapidly increasing in all regions of Iran, especially from central to western and southern regions. [ABSTRACT FROM AUTHOR]