Objective To provide a fever animal model for the study on the antipyretic mechanism of Ginseng Baihu decoction through replicating the fever model by using Rheum officinale and mirabilite decoction combined with intraperitoneal injection of lipopolysaccharide (LPS), and evaluating its immune function. Methods Wistar male rats were randomly divided into 0, 1, 3, 5, and 7 d gavage groups. They were respectively given Rheum officinale and mirabilite decoction by gastric irrigation for 0, 1, 3, 5, 7 d, and intraperitoneal injection of LPS was performed after the last time of administration by gastric irrigation. The feces state and body temperature changes of rats were observed and recorded. The fecal water content, spleen index, and blood cell count of blood samples were detected. Its objective is to analyze the impact of different days of Rheum officinale and mirabilite decoction given by gavage on the body temperature, feces moisture content, spleen index and blood cell number of rats induced by LPS. Results Compared with the 0 d group, the water content of the feces in the rats in the 1, 3, 5 and 7 d groups were increased, the number of leukocytes and neutrophils increased and the number of lymphocytes decreased, and the spleen index decreased. The number of leukocytes and neutrophils in the 5 d group were significantly increased compared with the 0, 1, 3, 7 d groups. The model of the 5 d group warmed up earliest, and its body temperature was the largest. Conclusion The traditional Chinese medicine Rheum officinale and mirabilite decoction combined with intraperitoneal injection of LPS can successfully establish a model of physical weakness and fever in accordance with the syndrome of Ginseng Baihu decoction. The body temperature, fecal water content and immune function of the model rats were closely related with the days of gastrointestinal administration of Rheum officinale and mirabilite decoction. Among them, the diarrhea and fever model of rat established by 5 d gavage is the best, and the model can be used for the study on the mechanism of antipyretic of Ginseng Baihu decoction.