Abstract: Objective: To study the anti-depressant effects of Acanthopanax senticosus and Coriolus versicolor ethanolic extracts in different proportions in mice, to screen out the proportion with the strongest anti-depressant activity, and explore its mechanism of action. Methods: The effective components were extracted by 75% ethanol with the ultrasound-assisted extraction method, and the mice were given the drug continuously for 14 days and the dose was 4.55 mg/kg. The effects of different proportions of Acanthopanax senticosus and Coriolus versicolor (1:1, 1:2, 1:3, 1:4, 1:5, 5:1, 4:1, 3:1, 2:1) ethanolic extracts on the behavior of mice were determined. Through intraperitoneal injection of reserpine, themice model of depression was established to detect the content of monoamine neurotransmitters in the brain of the mice and on serum IL-10 and IL-1β content in mice, so as to determine the effects of different proportion of Acanthopanax senticosus -Coriolus versicolor ethanolic extract on the depression effect of reserpine. Results: Different proportions of Acanthopanax senticosus and Coriolus versicolor (1:2, 1:1) ethanolic extracts markedly reduced immobility time in the tail suspension test (TST) and forced swimming test (FST) compared with the single drug group of mice (P<0.05), and they can inhibit the symptom of the hypothermia and ptosis caused by reserpine (P<0.05). Moreover, the research also found that the cotent of 5-hydroxytry ptamine (5-HT), norepinephrine (NE) were significantly increased (P < 0.01, P < 0.05) and IL-10 were significantly increased (P<0.01) in 1:2 groups. The best proportions of Acanthopanax senticosus and Coriolus versicolor ethanolic extracts was 1:2 (P<0.05). Conclusions: Acanthopanax senticosus and Coriolus versicolor ethanolic extracts possessed antidepressant effects in mice, which might be partially related to up-regulate IL-10, increase 5-HT, NE levels in the hippocampus and down-regulate IL-1β.