Objective:To test potential therapeutic effects of bisphosphonate nanoemulsion(BP nanoemulsion)in the experimental autoimmune neuritis(EAN). Methods:In vitro BP nanoemulsion treatment was performed in macrophage cell line RAW264.7,real-time PCR(RT-PCR)was used to evaluate the expression of inflammatory factors interleukin(IL)-1β,IL-6,inducible nitric oxide synthase(iNOS),anti-inflammatory factor IL-10 and macrophage M2 marker CD206. After successfully establishing EAN rats model,BP nanoemulsion treatment was given,weight change of rats was assessed. The mechanical pain threshold and clinical score were analyzed. Luxol fast blue(LFB)staining was applied to show sciatic myelinopathy. Inflammatory cell infiltration and pathological changes in the sciatic nerve were evaluated by immunohistochemistry. The expressions of inflammatory cytokines IL-1β,IL-17,iNOS and matrix metalloproteinase 9(MMP-9)mRNA level in sciatic nerve were detected by RT-PCR. Results:BP and BP nanoemulsion treatments inhibited IL-1β and iNOS,increased the expressions of IL-10 and CD206,and induced phenotypic switch of macrophage polarization from M1 to M2 subtype in cell culture. In EAN rats:BP nanoemulsion ameliorated body weight loss and neurological signs,ameliorated mechanical allodynia,shortened disease duration,reduced myelin lesions. Meanwhile,it inhibited accumulation of macrophages and other immune cells,and decreased expressions of inflammatory cytokines IL-1β,IL-17,iNOS,and MMP-9 mRNA level in sciatic nerves of EAN rats. Conclusion:BP nanoemulsion can reduce accumulation of immune cells and attenuated inflammatory cytokines in sciatic nerves,and improve the clinical pathological changes of EAN rats. BP nanoemulsion may therefore be considered a potential therapeutic option for neuroinflammatory diseases.