Objective: To study the antidepressant effect of Anacycli Pyrethri Radix extract (APRE) in chronic unpredictable mild stress (CUMS) model and drug-induced depression model. Methods: The chronic unpredictable stimulus was used to establish exogenous chronic stress depression model in rats. The sucrose preference, open-field test, forced swimming test and tail suspension test were used to observe the behavioral changes of rats. Serum levels of corticosterone and 5-HT and DA of hippocampus were analyzed using ELISA. Reserpine reversal test, 5-HTP induced head-twitches test and yohimbine induced lethality were used to establish endogenous mouse depression model; Blepharoptosis, akinesia, head-twitch cunts and mortality were observed to study he antidepressant effect of APRE. Results: In the chronic unpredictable stress model, APRE could increase the sucrose intake, crossing numbers and rearing numbers obviously, the immobility time was reduced, the level of the serum corticosterone was reduced significantly, the 5-HT and DA of hippocampus were increased. In the drug-induced depression model, blepharoptosis and akinesia incuced by reserpine were inhibited, head-twitches induced by 5-HTP was significantly increased, but there was no effect on mortality induced by yohimbine. Conclusion: APRE has obvious antidepressant effect possibly by decreasing corticosterone level and promoting 5-HT nerve function. © 2017, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.