Objective To reveal the distribution and effects of peripheral nerve axolemma ion channels in experimental allergic neuritis (EAN). Methods The alteration of Na+ and K+ channels on peripheral nerves (PNs) in the course of EAN was observed and the relationship between the channels and nerve conduction properties was analyzed by assessing histology and electrophysiology of PNs as well as clinical severity. Results Na+ and K+ channels obviously decreased on day 9 post immunization (p.i.), a time point of disease onset, and quickly became undetectable in next two weeks. Undergoing a slow and incomplete regeneration, neither of the channels regained the normal appearance on day 85 p.i. even if the clinical symptom disappeared several weeks before. Na+ and K+ channels had a synchronous development during disease course and remained a close correlation with the alteration of paranodal myelin. Electrophysiological abnormality kept consistent with the disturbance of PNs just in the acute period of EAN (923d p.i.) and the compound muscle action potential (CMAP) amplitude partly reflected the distribution of axolemma ion channels. Conclusion Loss of axolemma ion channels of PNs might be one of the reasons directly leading to the early symptoms of EAN. As a structural component, the channels were liable to damage and difficult to restore. The clustering and maint