AIM: To explore the therapeutic strategies of heat-clearing and detoxifying (HCDT) and Yin-invigorating and fluid-supplementing (YIFS), the method of Chinese medicine, on the high density lipoprotein (HDL) and alkaline phosphatase (ALP) molecules, which are associated with endotoxin-degradation. METHODS: The animal model of endotoxemia was established by the injection of E. Coli lipopolysaccharides through rabbits ear vein. The endotoxemic rabbits were treated respectively with two representative herbal preparations of therapeutic principles against febrile diseases: HCDT or YIFS preparations. The serum levels of interleukin-1 (IL-1), tumor necrosis factor ? (TNF-?) and HDL, the ALP activity, the expression of ALP mRNA in liver and kidney tissues were observed. RESULTS: The serum levels of IL-1 and TNF-? in HCDT group were significantly decreased, while the serum ALP activity and the expression of ALP mRNA in liver and kidney tissues were obviously increased, as compared with those in model group. Meanwhile, the serum levels of IL-1 and TNF-? in YIFS group were significantly reduced, and its plasma HDL level was elevated. CONCLUSIONS: Both the herbal preparations, HCDT and YIFS, have the scavenging effects on the overproduction of inflammatory cytokines such as IL-1 and TNF-? induced by endotoxin, but their effects on the endotoxin-degrading molecules might be different. HCDT principally increases ALP activity and enhances ALP expression in liver and kidney tissues, while YIFS might preferably facilitate the elevation of plasma HDL level.