Abstract: Objective 　To adverse reaction of Cancer Rening suppository in the t reatment of fever cancer. Methods 　The models of noninfected fever induced by 2, 42binit ro2phenol was used to observe the changes of temperature in different time, TNF2αand IL21βin the serum of rabbit were determined by double anti2 bodies sandwich Enzymelinked Immurosorbent Assay. Immuno2histochemical assay was used to detect the expression between PKA activities of hypothalamus and the changes of temperature. Results 　Different doses of Cancer Rening suppository (13. 5 g/ kg, 4. 5 g/ kg, 1. 5 g/ kg) reduced the febrile responses of rab2 bit induced by noninfected fever. In the febrifuge experiment of rabbit, both the high and middle group have the febrifuge effect obviously. Changes of TNF2α、IL21βin serum and PKA in hypothalamus during noninfected fever induced by 2, 42binit ro2phenol in rabbit s are significantly increased. Cancer Rening sup2 pository has a protective effect on noninfected fever induced by 2, 42binit ro2phenol in rabbit s, decreasing the expression of TNF2α、IL21βin serum and PKA in hypothalamus obviously. Correlation analysis indica2 ted that the changes of the rabbit body temperature were positively correlated with the content s change of PKA in the hypothalamus of the five rabbit group s. Conclusion 　The antipyretic mechanisms of Cancer Rening suppository may be related to it s decreasing the content s of TNF2α、IL21βin serum and PKA in hypothalamus. It may be an important antipyretic mechanism of Cancer Rening suppository.