Objective To investigate the effect of atorvastatin on myelin repair and the RhoA/ Rock1 pathway in mice with autoimmune encephalomyelitis (EAE). Methods MOG35-55 immunization was used to establish an EAE mouse model. The mice were randomly divided into the control group, model group, atorvastatin group, high fat diet group and high fat diet+atorvastatin group ( n= 6 per group). The atorvastatin was administered to each mouse daily by 0. 5 mL suspension, for 28 consecutive days. Mice were scored for neurological function and clinical symptoms were observed. Hematoxylin-eosin ( HE ) staining, Luxol fast blue ( LFB ) staining, transmission electron microscopy and immunohistochemical staining method were used to detect inflammation and demyelination and remyelination of the spinal cord tissue of each group of mice. The expression of tumor necrosis factor-α (TNF-α), interleukin-6 ( IL-6) and nitric oxide (NO) in serum was detected by enzyme linked immunosorbent assay (ELISA); protein immanoblotting assay(Western blot) method was used to detect the expression of Ras homologous gene family member A (RhoA) and Rho associated protein kinase 1 (ROCK1) in brain tissue. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression of chondroitin sulfate proteoglycan ( NG2) and myelin basic protein ( MBP) in spinal cord and RhoA and Rock1 mRNA expression in brain tissue. Results Compared with the control group, the model group showed more inflammatory cell infiltration, marked demyelination, partial myelination disintegration, breakage and demyelination; TNF-α, IL-6 and NO in serum and the expression of RhoA, Rock1 protein and mRNA in brain tissue were significantly increased, while the expression levels of NG2 and MBP protein and mRNA in spinal cord tissue were significantly decreased (P<0. 01). Compared with the model group, the atorvastatin group showed significant improvement in inflammatory cell infiltration and demyelination, significantly decreased TNF-α, IL-6 and NO in serum, expression of RhoA and Rock1 protein and mRNA in brain tissue and increased expression of MBP, NG2 protein and mRNA in brain tissue (P< 0. 05). The high fat diet + atorvastatin group showed significantly decreased neurological function scores, brain tissue RhoA and Rock1 expression and significantly increased NG2 mRNA expression. Conclusions Atorvastatin improved inflammatory cell infiltration and demyelination in EAE mice and reduced neurological function scores in EAE mice on a high fat diet. The mechanism of action may be related to the regulation of the RhoA/ Rock1 pathway to improve the degree of demyelination and thus exert a therapeutic effect on EAE mice.