Abstract: OBJECTIVE  To explore the relationship between the antipyretic activity and chemical quality control components of Reduning Injection(RDN).METHODS  RDN was administered on lipopolysaccharide(LPS)-induced fever rats to observe the antipyretic effect and detect the level of PGE₂ in hypothalamus tissue. LPS-induced RAW 264.7 cells were replicated and cyclooxygenase(COX)-2 enzyme assay were performed to evaluate the activity of RDN and its chemical components against PGE ₂ and COX-2.RESULTS  RDN could obviously reduce the temperature rise in fever rats, and PGE₂ level in hypothalamus tissues. RDN could also inhibit the release of PGE₂ and the activity of COX-2, with IC₅₀ of 27.07 μg/mL, 418.6 ng/mL, respectively. Meanwhile, the level of PGE₂ was reduced by caffeic acid, neochlorogenci acid and isochlorogenic acid A, isochlorogenic acid B, while the activity of COX-2 was inhibited by chlorogenic acid, crytochlorogenic acid, caffeic acid and isochlorogenic acid A, isochlorogenic acid B, isochlorogenic acid C.CONCLUSION  RDN shows significant antipyretic effect via inhibiting the activity of COX-2 and reducing the release of PGE₂, which was related to caffeolyquinic acids in chemical quality control indexes.