In order to clarify the protective effect of bilobalide(BB)on depressed mice as well as its mechanism,BB with a purity of 98.21%was prepared from 40%BB by molecular imprinting solid phase extraction(MISPE).Thirty-six ICR mice aged six-to-eight weeks were randomly divided into six groups:control group,model group,fluoxetine group(10 mg/kg),low,middle and high dose groups of BB(3.5,7.0 and 14.0 mg/kg).Except for the control group,the depression models of mice were established by chronic unpredictable mild stress(CUMS)model.In the course of the experi-ment,the changes of depression in mice after BB intervention were observed,and the body weight of mice was recorded.At the end of the experiment,the contents of inflammatory factors in serum,monoamine neurotransmitters in brain and brain-derived neurotrophic factor(BDNF)in hippocampus were measured.The results showed that BB could improve the depression of mice,significantly re-duce the contents of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6),increase the contents of monoamine neurotransmitters dopamine(DA),norepinephrine(NE)and serotonin(5-HT),and pro-mote the expression of BDNF.In general,BB can play a protective role in depressed mice by inhibi-ting inflammation,promoting the production of monoamine neurotransmitters in brain and promoting the expression of BDNF.