OBJECTIVE To screen the effective anti-depressant part from Coreopsis tinctoria and study its mechanism. METHODS The anti-depressant effects of 30％，50％，70％ and 90％ ethanol elution fractions from 75％ ethanol extract of C. tinctoria（CCTE）were investigated by tail suspension test and forced swimming test. Mice head-drop test ，reserpine antagonistic test，yohimbine toxicity enhancement test and in vitro monoamine oxidase （MAO） inhibition test were used to explore the mechanism of the relationship between the effective parts and 5-hydroxytryptamine （5-HT） and norepinephrine （NE） nerves. RESULTS The 50％ and 70％CCTE could significantly shorten the accumulative immobility time in tail suspension test and forced swimming test （P＜0.05 or P＜0.01），increase the number of head-shaking times （P＜0.01），reverse the eyelid ptosis ， hypothermia and immobility caused by hematopin （P＜0.05 or P＜0.01），and increase the number of dead mice caused by yohimbine toxicity （P＜0.01）. IC 50 of okanin （CCT-6），isookanin（CCT-7）and taxifolin （CCT-8）against MAO were 8.71，37.89 and 67.07 µmol/L，respectively. CONCLUSIONS The 50％ and 70％CCTE are the effective anti-depressant parts of C. tinctoria . Its anti-depressant effect may be related to the reinforcement of 5-HT and the activation of NE nerves. The inhibition of CCT- 6， CCT-7 and CCT- 8 against MAO may be one of the anti-depressant mechanism of C. tinctoria .