Shuang-Huang-Lian (SHL), a famous traditional Chinese medicine recipe containing Lonicerae Japonicae Flos (LJF), Forsythiae Fructus, and Scutellariae Radix, is clinically used for the treatment of fever and acute upper respiratory tract infection. In this research, a comparative study was conducted to compare the pharmacokinetic difference of chlorogenic acid (ChA) after oral administration of LJF and SHL to normal and febrile rats with approximately the same dose of 60 mg/kg, and the antipyrexia effect of LJF and SHL on rectal temperature changes induced by Baker's yeast was investigated. The results indicated that AUC0 − t and plasma concentrations of ChA in the febrile rats were significantly higher than normal rats whether in the extract of LJF or SHL. In addition, SHL increased the values of AUC of ChA in both febrile and normal rats compared with LJF alone (p < 0.05), and SHL showed better antipyrexia effect than LJF. These results indicate that fever could play an important role in pharmacokinetic process of ChA. Meanwhile, the combined formula SHL exhibits higher bioavailability of ChA and superior antipyrexia effect than the single herb. Copyright © 2013 John Wiley & Sons, Ltd.