Objective To investigate the effect of glycyrrhizin compound (CG) on mouse models of experimental autoimmune encephalomyelitis (EAE) via the JAK2 / STAT3 / SOCS3 signaling pathway. Methods Fifty female C57BL/ 6 mice were randomly divided into the control group, model group, and high-dose, medium-dose and low-dose CG intervention groups (n = 10 mice per group). The model and CG intervention groups established the EAE model. The intervention groups were injected with CG (15 mg / (kg·d), 30 mg / (kg·d), or 60 mg / (kg·d)) for 14 consecutive days. The control and model groups were simultaneously intraperitoneally injected with equal volumes of saline. The neurological deficit scores and pathological changes in each group were recorded. Western blot was used to detect protein expression in the brain tissue, and real-time fluorescence quantitative RT-PCR was used to detect mRNA expression in the brain tissue. Results Compared with the model group, the highest neurological deficit and cumulative neurological deficit scores were reduced, spinal cord inflammation and demyelination were reduced, JAK2 and STAT3 protein and mRNA expressions were decreased, SOCS3 protein and mRNA expressions were increased, RORγt mRNA expression was decreased, and FOXP3 mRNA expression was increased in all CG groups ( all P < 0. 05). Conclusions CG exerted preventive and therapeutic effects on EAE model mice. The mechanism may be related to upregulation of SOCS3, inhibition of the JAK/ STAT signaling pathway, and rectification of the Th17 / Treg immune imbalance.