Multiple sclerosis (MS) was induced in mice by cuprizone 0.2% (w/w) for five successive weeks, then mice were divided into five groups, first group was normal mice, second group was MS-induced mice, third group was MS-induced mice treated by a single intraperitoneal dose of microvesicles (0.2 mg/kg), fourth group was MS-induced mice treated by a single intraperitoneal dose of melatonin (10 mg/kg) for three successive weeks, and fifth group was MS-induced mice treated by combination of microvesicles and melatonin. Behavioural functions were evaluated by rotarod test, activity cage and Y-maze. We also measured levels of situin1, sirtuin 3, PGC-1 alpha, complex I, complex II, ATP, MDA, GSH, miRNA 155 and 132. Finally, histological and immunohistochemical examinations of the corpus callosum were performed. Results showed impaired behavioural functions, as well as decreased levels of sirtuin 1, sirtuin 3, PGC-1 alpha, complex I, complex II, ATP and GSH, also increased levels of MDA, miRNA 155 and 132 in MS-induced mice. The behavioural and biochemical parameters mostly returned to normal with treatment using melatonin and microvesicles. Histological examination of the cuprizone treated group revealed loss of normal histological profile. However, a single or combined treatment with microvesicles therapy or melatonin revealed substantial improvement