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Objective To investigate the role of myelin protein zero (P0) in 2,5-hexanedione (2,5-HD)-induced peripheral nerve injury,and the protective effect of Ginkgo biloba extract (Egb761) on 2,5-HD-induced toxic peripheral neuropathy.Methods After 4 weeks of treatment with 2,5-HD at different doses (50,100,200,400 mg/kg) in rats,changes in the levels of P0 in rat sciatic nerves was investigated,and the effect of Egb761 on 2,5-HD-induced toxic peripheral neuropathy was studied.Results The blood-nerve barrier (BNB) permeability of the sciatic nerve increased,and the expression of P0 mRNA and P0 protein decreased in a dose-dependent manner after treatment with 2,5-HD for 4 weeks.Pretreatment with Egb761 protected against BNB interruption,and inhibited P0 mRNA and protein reduction during 2,5-HD treatment.Pretreatment with Egb761 significantly reduced loss of body weight (P＜0.01) and mitigated gait abnormalities (2.85±0.22) induced by 400 mg/kg 2,5-HD (P＜0.01).It also reduced the signs of neurotoxicity induced by 2,5-HD.Conclusion 2,5-HD inhibited the expression of P0 in a dose-dependent manner,and this may be an important mechanism by which toxic peripheral neuropathy is induced by 2,5-HD.Egb761 has a protective effect against 2,5-HD-induced peripheral neurotoxicity in rats.