OBJECTIVE Nowadays, an increasing number of people are suffering affective disorder.Althogh several types of classical antidepressents have used in clinical which causes undesirable side effects their mechanisms of action have not been satisfactorily resolved.It is really urgent that we should seek effective and safe antidepressant agents.Our present study was to examine the anti-depressant like effect of fisetin in mouse behavioral despair tasks and investigate the possible mechanism of monoaminergics in the anti-depressant-like effect though various behavioral paradigms.METHODS 1.Behavioral tests : (1) Tail suspension test (2) Foced swimming test.During these two tests, the time which mice spend on remaining immobile was recorded in 6min.(3) Locomotor activity.We tested the locomotion counts to excluding the excitatory or inhibitory effects after administration of various drugs.(4) PCPA test (5) Reserpine test 2.Biochemical indicator: (1) Determination of monoamines and metabolities: The contents of 5-HT, 5-HIAA, NA, DA and DOPAC were measured as described previously using high-performance liquid chromatography (HPLC) with eletrochemical detection with minor modifications.(2) Measurements of monoamine oxidase activity : Monoamine oxidase activity was expressed as nmol of 4-hydroxyquinoline formed/30 min/mg protein.RESULTS From what we have done above, we may discovered that fisetin (10 and 20 mg·kg-1, via gavage) produce a significant inhibition in the recorded immoblity time of mice performing the forced swimming and tail suspension tests, with comparable profiles to that observed for the classical antidepressants imipramine.Three monoamines 5-HT and NA levels were significantly increased after fisetin, imipramine (10 mg·kg-1) administration.Fisetin also exhibited a tendency to decrease the measured 5-HIAA/5-HT levels.CONCLUSION These results suggested that fisetin, at the same doses that produce an antidepressant-like effect, did not show significant locomotor stimulation.And these effects of fisetin may involve the central monoaminergic neurotransmitter systems.