AbstractObjectiveMultiple sclerosis (MS) is a central nervous system disorder characterized by inflammation, demyelination and neurodegeneration. It has been suggested that exercise and intake of probiotics might influence MS pathology and, thereby, slow down the disease process in MS patients. Therefore, this study aimed to investigate the effect of exercise training with Lactobacillus plantarum intake on ionized calcium‐binding adaptor molecule 1, glial fibrillary acidic protein, interleukin (IL)‐6 and IL‐1β in cuprizone‐induced demyelination mouse model of MS.MethodsMice were exposed to cuprizone for 13 weeks. In the fifth week, motor and balance tests were carried out on them. The mice (n = 5 per group) were randomly divided into five groups: control (C), MS, MS with exercise (MS + Exe), MS with probiotics (MS + Pro) and MS with probiotics and exercise (MS + Pro + Exe). The exercise groups carried out aerobic exercises 5 days a week for 2 months. The mice received probiotic by gavage. One day after the interventions finished, the mice were killed. Biochemical and molecular biology analyses were carried out.ResultsIonized calcium‐binding adaptor molecule 1 and glial fibrillary acidic protein expression values in the MS + Pro + Exe, MS + Pro, and MS + Exe groups showed a significant decrease compared with the MS group (P < .05). Also, glial fibrillary acidic protein gene expression in the intervention groups showed an insignificant decrease (P > .05). The IL‐6 and IL‐1β values in the MS + Exe and MS + Pro + Exe groups showed a significant decrease compared with the MS group (P < .05).ConclusionsExercise with the intake of probiotics improved demyelination in the cuprizone‐induced demyelination mouse model of MS.