Objective To study antidepressant effect and mechanism of different polar fraction of Acorus tatarinowii Schott.on depression mouse model and explore the mechanism. Methods Different polar fractions were prepared by systematic solvent method. The adult dose recommended by Chinese Pharmacopeia ( 10 g?d-1 ) was converted to the dose of mouse. Intragastric administration was performed.A total of 80 male mice was randomly divided into normal control group,model control group and different polar fraction groups of Acorus tatarinowii Schott.. Depression mouse model was established by chronic unpredictable mild stimulation ( CUMS) with solitary feeding,and external performance of mice of different groups was observed. After 21-day feeding,blood was harvested from eyes of the mice.Concentrations of triiodothyronine (T3),tetraiodothyronine (T4), thyroid-stimulating hormone ( TSH) ,adrenocorticotrophic hormone ( ACTH) in mouse plasma and 5-hydroxy tryptamine ( 5-HT) , ACTH in brain were measured by ELISA method. Results Concentrations of T3 , T4 and ACTH in model control group [(1.203±0.042),(44.80±2.21),(11.27±0.50) ng?mL-1] were significantly increased as compared with the normal control group [(0.794±0.028),(24.87±1.25),(7.04±0.24) ng?mL-1] (P<0.05).Concentration of 5-HT in brain (146.87±10.96) was significantly decreased as compared with that of normal group ( 237. 11 ± 21. 87 ) ng?L-1 , and concentration of ACTH (58.94±4.46) ng?L-1 was significantly increased as compared with that of normal group [(38.89±2.26) ng?L-1,P<0.05)]. Concentrations of T3[(0.824±0.067),(0.812±0.051),(0.943±0.049) ng?mL-1],T4[(25.97±1.96),(27.53±1.88), (31.26±1.97) ng?mL-1] and ACTH [(7.21±0.40),(7.58±0.39),(8.69±0.42) ng?mL-1] in extraction group,cyclohexane group and chloroform group were significantly decreased as compared with model control group. At the recommendation dose of Chinese Pharmacopeia,concentrations of 5-HT in brain [(219.59±10.48),(202.19±11.95),(186.96±10.29) ng?L-1] were significantly increased,and concentrations of ACTH [(41.65±2.65),(44.87±2.95),(47.75±3.06) ng?L-1] were decreased ( P<0.05) . Conclusion Mouse model of CUMS shows typical depression symptom,and the symptom has relationship with the concentrations of endocrine hormones of T3 , T4 , ACTH, 5-HT, etc. Extraction and low polar fractions ( cyclohexane, and chloroform) of Acorus tatarinowii Schott. can partly correct incretion disorder of depression model, which may be parts of the reasons why Acorus tatarinowii Schott.exerts anti-depressant effect.