Based on in vivo experiments combined with network pharmacology and metabolomics, the antipyretic mechanism and possible antipyretic constituents of BHT were investigated; the research outcome of this study will scientifically suggest that the peripheral antipyretic mechanism of BHT may be partly due to the inhibition of the endogenous thermogen TNF-α, preventing LPS-induced fever, and provide pharmacological interpretations in the traditional use of BHT. The gene discussed is TNF; the disease is Fever.