Abstract: OBJECTIVE To study the antidepressant effect of kaempferol on rat complex model of depression and breast cancer. METHODS The rats were randomly divided into six parts including the control group, depression model group, breast cancer model group, complex model group, fluoxetine administration group, kaempferol administration group, respectively. The rat depression model was established by the method of chronic unpredictable mild stress. The breast cancer model was induced by dimethylbenzanthracine(DMBA). The open filed test was used to evaluate the autonomic activities. The LC-MS/MS method was used to assay the levels of monoamine neurotransmitters including norepinephrine (NE), serotonin (5-HT) and dopamine (DA) in the hippocampal area and the prefrontal cortex. RESULTS There were no significant differences in the open-field test between the cancer group and normal group, whereas the open-field activities decreased significantly in the depression model group and complex model group including horizontal movements and vertical movements with comparison to the normal group (P<0.01). The autonomic activities increased significantly after kaempferol administration (P<0.01 or P<0.05). The antidepressant-like effect of kaempferol was similar to fluoxetine with respect to increasing the autonomic activities. The levels of NE, DA and 5-HT in the brains of the depression model and complex model showed to decrease comparing to the control group. whereas the levels of those in kaempferol administration group were higher than those in the complex model group. And the levels of DA, NE and 5-HT in the prefrontal cortex were significantly increased (P<0.01 or P<0.05). These changes were almost observed in fluoxetine administration group. CONCLUSION The study suggested that kaempferol showed antidepressant effects on rat complex model of depression and breast cancer. The underling mechanism of kaempferol antidepressant effect may be associated with increased the level of monoamine neurotransmitters in rat prefrontal lobe.