Abstract: Objective:To establish a herpes simplex virus encephalitis(HSE) model in Balb/c mouse.Methods:Forty Balb/c mice were intracerebrally or intranasally inoculated with(herpes simplex virus type 1,HSV-1)F strain 104 plaque forming unit(PFU,titer=3.5105/ml),another twenty mice were intracerebrally or intranasally inoculated with saline as control,separately.The ethological and pathological changes were evaluated.Results:The Balb/c mouse which intracerebrally inoculated with HSV-1 exhibited different symptoms such as hair disorder,downcast,agitation,seizure and death,etc.These mice showed clinical feature as early as 3 days after inoculation,which reached peak at 7-10 days,and recovered after 14 days.Some mice were died at the 6th day.The pathological changes included inflammatory cell infiltration of meninges and parenchyma,neurons necrosis,lymphocytic muff around the vessel and microglia proliferation,etc.Only one mouse in intranasal inoculation group was shown mild hair disorder.The ethological and pathological changes were not observed in each control group.The morbidity of intracerebral inoculation group was obviously higher than the intranasal inoculation group and the control group(P0.01).Conclusions:Inoculation of HSV-1 F strain 104 PFU in Balb/c mouse intracerebrally can establish a stable HSE model.