To investigate the effect of Qingre Sanyu Jiedu decoction on cAMP of rats with EP induced fever. Methods: Rats were divided into the model group (n=12), Chinese medicine group (n=12), western medicine group (n=12). Rats in each group were injected with 2, 4-dinitrophenol to establish fever models. A normal group (n=6) was included in study. The normal group and model group were injected with saline, while Chinese medicine group and western medicine group were respectively injected with Qingre Sanyu Jiedu decoction and naproxen. The body temperature and the concentration of cAMP in serum and hypothalamus were measured two hours after injection. Results: The temperature of Chinese medicine group and western medicine group were lower than those of the model group. cAMP content in serum and hypothalamus of the Chinese medicine group and western medicine group were lower than vehicle group, which all showed statistical significance (P<0.05). Conclusion: Qingre Sanyu Jiedu decoction may have the function of reducing temperature, and its mechanism may be related to the reduction of cAMP content in rat serum and hypothalamus.