Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate the antipyretic and anti-inflammatory activities of T. luteostoma. T. luteostoma was divided into shell(TLSH) and soft tissue(TLST) samples in the present study. The rat model of yeast-induced fever was used to investigate their antipyretic effects; and the rat model of hind paw edema induced by carrageenan was utilized to study their anti-inflammatory activities, and at the same time, the concentration variations of the central neurotransmitter [prostaglandin E2(PGE2) and cyclic adenosine monophosphate(cA MP)], inflammatory mediators [tumor necrosis factor(TNFα), interleukin-1β(IL-1), interleukin-2(IL-2) and interleukin-6(IL-6)] and ion(Na+ and Ca2+) were also tested. The results showed that TLSH and TLST extracts significantly inhibited yeast-induced pyrexia in rats(P < 0.05), and exhibited more lasting effects as compared to aspirin, and TLSH had the better antipyretic activity than TLST, and that TLSH and TLST could significantly prevent against carrageenan induced paw edema in rats(P < 0.05); and markedly reduced levels of PGE2, cA MP, TNFα, IL-1β, IL-2, IL-6, and Na+/Ca2+. In fever model, TLST could significantly reduce the levels of PGE2(P < 0.01) in rats’ homogenate and TNFα(P < 0.05), IL-1β(P < 0.01) in the plasma than TLSH, whereas TLSH could reduce the content of IL-2(P < 0.01) and IL-6(P < 0.01) in plasma and increase the content of Ca2+(P < 0.01) in plasma and homogenate more significantly than TLST. In conclusion, T. luteostoma extract has antipyretic and anti-inflammatory activities, which may be mediated through the suppression of production of PGE2, c AMP, Na+/Ca2+, TNFα, IL-1β, IL-2, and IL-6. Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate the antipyretic and anti-inflammatory activities of T. luteostoma. The rat model of yeast-induced fever was used to investigate their antipyretic effects; and the rat model of hind paw edema induced by carrageenan was (TLSH) and soft tissue (TLST) samples in the present study utilized to study their anti-inflammatory activities, and at the same time, the concentration variations of the central neurotransmitter [prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cA MP)], inflammatory mediators [tumor necrosis factor (TNFα) The results showed that TLSH and TLST extracts significantly inhibited yeast-induced pyrexia (IL-1), interleukin-2 (IL-2) and interleukin- in rats (P < 0.05), and showed more lasting effects as compared to aspirin, and TLSH had the better antipyretic activity than TLST, and that TLSH and TLST could significantly prevent against carrageenan-induced paw edema in rats (P <0.05); and markedly reduced levels of PGE2 (P <0.01) in rats’ homogenate and TNFα (P <0.05), cA MP, TNFα, IL-1β, IL-2, IL-6, and Na + / Ca2 + (P <0.01) in plasma and increase the content of Ca2 + (P <0.01) in the plasma than TLSH, whereas TLSH could reduce the content of IL-2 In conclusion, T. luteostoma extract has antipyretic and anti-inflammatory activities, which may be mediated through the suppression of production of PGE2, c AMP, Na + / Ca2 +, TNFα, IL- 1β, IL-2, and IL-6.