Japanese encephalitis (JE) is an acute encephalitis syndrome contributed to Japanese encephalitis virus (JEV) infection. It is the chief cause of viral encephalitis in Asian. In recent years, association of JEV infection with neurological problems such as Guillain-Barré syndrome had reported. Nevertheless, its potential pathogenic mechanism has never been reported. Therefore, it is urgent to explore the relationship between peripheral nerve injury and JEV infection. Here, we use the liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique to make out the protein expression levels of mice sciatic nerve between JEV infection group and the sham group. In general, 4303 proteins were identified by MS, and 187 differentially expressed proteins were found. There were 105 proteins up-regulated in the injured sciatic nerve, and 82 proteins were down-regulated. Functional enrichment analysis of differentially expressed proteins showed that the up-regulated proteins were mainly related to immune regulatory response, and the down-regulated proteins were related to ribosomal structural components and translation.