To explore the antipyretic action and mechanism of Astragalus complying with different dosages of Radix Bupleuri on the rat models of spleen-qi deficiency with fever. Methods: The male wistar rats were randomly assigned to the normal group, the spleen-qi deficiency with fever group, the astragalus with large dosage radix bupleuri group, the astragalus with medium dosage radix bupleuri group, the astragalus with small dosage radix bupleuri group, and the radix bupleuri group. The model rats of spleen-qi deficiency were prepared through excess fatigue and out of constant diet for 21 days. The medicine group rats were fed with 4.56g/kg (large), 2.95g/kg (medium) 2.41g/kg (small) and 2.41g/kg (radix bupleuri only) once a day and the other two groups were given physiological saline from the seventeenth day. At 8: 00 am on the 22th day，the rats of model group and medicine groups were respectively intraperitonealy injected with lipopoly saccharide( LPS, 8 0 μg/kg) to induce fever．The rats of the normal group were given physiological saline．The rectal temperature was measured at different time after ip LPS. And then the amounts of cytokines in blood and transmitters which regulate temperature in hypothalamus were also measured．Results: Compared with the normal group，the temperature of rats in the spleen-qi deficiency with fever group raised to some extent at every observation time after ip LPS, especially at 60min and 220min（P<0.05）. IL-2 in blood、CAMP and PGE2 in hypothalamus increased significantly（P<0.05）. AVP in hypothalamus had decreased. Compared with the spleen-qi deficiency with fever group, the temperature of rats in every medicine group decreased significantly to some extent（P<0.05）. CAMP and PGE2 in hypothalamus increased or decreased（P<0.05）. The temperature declined and IL-1βin hypothalamus decreased significantly（P<0.05）in the radix bupleuri group and the astragalus with small dosage radix bupleuri group. Blood of IL-1β increased significantly（P<0.05）in the astragalus with large dosage radix bupleuri group. Compared with the astragalus with large dosage radix bupleuri group, blood IL-1β decreased significantly（P<0.05）in the astragalus with medium and with small dosage radix bupleuri groups, as well as the radix bupleuri group. Blood IL-2 increased significantly（P<0.05）in the astragalus with medium and with small dosage radix bupleuri groups. Conclusion: Astragalus complying with different dosage of radix bupleuri and only application of large dosage of radix bupleuri had antipyretic effect to the model rat of spleen-qi deficiency with fever. Its antipyretic mechanism may be connected with reducing central pyrexia amboceptor PGE2 and increasing AVP. And astragalus complying with small dosage of radix bupleuri and the only application of large dosage radix bupleuri may be also related to declining of central IL-1β.