Objective To explore the effect of cannabinoid 1 receptor (CB1R) overexpression on the neurological function of mice with experimental autoimmune encephalomyelitis (EAE) and the related mechanism. Methods Twenty-four C57B/L6 mice were selected to prepare EAE models by MOG_35-55 immunization and were divided into two groups. CB1R was overexpressed in mouse spinal cord tissue by plasmid transfection technique in CB1R overexpression group, and the other group was given solvent as control. The neurological deficits of mice were observed in control group and CB1R overexpression group. The expression of CB1R in the spinal cord of mice were detected by Western blotting analysis. The concentrations of interleukin (IL)-10, IL-17, IL-6, and tumor necrosis factor-α (TNF-α) were measured by ELISA. Results The degree of neurological deficit of mice in the CB1R overexpression group was significantly lower than that in the control group on 14^th and 28^th day after immunization (P <0.05). Compared with the control group, the expression of CB1R protein in spinal cord in the CB1R overexpressing group was significantly increased (P <0.01), the concentration of IL-10 was significantly increased (P <0.05), and the concentrations of IL-17, IL-6, and TNF-α were significantly decreased (P <0.05, P <0.01). Conclusion CB1R overexpression in central nervous cells can postpone the development and progression of EAE in mice, which may be achieved through immuomodulation.