Neurodegenerative processes play an important role in the progression of MS. Appropriate exercise training and living in an enriched environment (EE) can improve or prevent the progression of the disease through the secretion of some neurodevelopmental factors in the hippocampus, including irisin and the neutrophic factor derived from the mouse. The aim of the present study was to investigate the effect of 4 weeks of aerobic and resistance training and EE on irisin protein and hippocampus BDNF levels in female C57BL6 mice with experimental autoimmune encephalomyelitis (EAE). 50 female mice (age 8 weeks, average weight 18 ± 2 grams) were randomly divided into five equal groups (10 mice in each group): 1- healthy control, 2- control + EAE, 3- resistance activity + EAE, 4- Aerobic activity + EAE and 5- EE + EAE. The first and second weeks of adaptation to the environment and then induction of EAE were performed. The training groups trained 5 days a week for half an hour a day for 4 weeks, and the EE group was transferred to its equipped cage. 48 hours after the last training session, the mice were anesthetized and then dissected and tissue removed. The ELISA method was used to measure the amounts of proteins, and the analysis of variance and Tukey's t-test were used to determine the differences between the research variables. All analyzes were performed at a significance level of 0.05 and with SPSS22 software. Hippocampal BDNF expression was increased in all three training groups compared to the EAE control group. This increase in the EE and resistance training group was significant compared to both the EAE control group and the swimming training group. Also, hippocampal irisin expression increased in all three training groups compared to the EAE control group, and this increase was significant in the EE and resistance training groups. Also, the expression of irisin in the EE group increased more than the two aerobic swimming and resistance training groups, and this increase was proportional to It was meaningful to the swimming aerobic training group. It seems that EE and resistance training can increase the secretion of nerve growth factors such as irisin and BDNF and thus help to improve MS disease.