Abstract: OBJECTIVE To analyze the effect of Zedoary turmeric oil on the expression of TNF-α, TLR2 mRNA and S100B proteins in mice with viral encephalitis and to explore the mechanism of Zedoary turmeric oil in the treatment of herpes simplex viral encephalitis(HSE). METHODS Forty New Zealand male mice aged 5 weeks were randomly divided into blank control group, Zedoary turmeric oil group, herpes simplex virus(HSV)-1 group, HSV-1+Zedoary turmeric oil group. HSV-1 group and HSV-1+Zedoary turmeric oil group were injected intracranial HSV-1 to make HSE model, and the blank control group and Zedoary turmeric oil group were injected with Vero cell culture medium supernatant in the same way. After modeling, blank control group and HSV-1 group were given normal saline, Zedoary turmeric oil group and HSV-1+Zedoary turmeric oil group were given Zedoary turmeric oil. The pathological changes of brain tissues were analyzed by immunohistochemistry, the levels of TNF-α and S100B in brain tissues were detected by ELISA, and the levels of TLR2 mRNA in brain tissues were detected by QT-PCR. RESULTS Compared with HSV-1 group, HSV-1+Zedoary turmeric oil group showed that the degeneration and edema of brain parenchyma cells decreased, and the invasion and infiltration level of monocyle macrophages such as lymplogyles and microglia in brain lesions decreased. Compared with HSV-1 group, the levels of TLR2 mRNA in HSV-1+Zedoary turmeric oil group were significantly lower(P<0.01). The levels of TNF-α and S100B in HSV-1+Zedoary turmeric oil group were significantly lower than those in HSV-1 group(P<0.01). CONCLUSION Zedoary turmeric oil may exert its therapeutic effect by inhibiting the expression of TNF-α, TLR2 mRNA and S100B protein in mice with viral encephalitis.