Objective To establish a humanized mouse model of depression by fecal bacteria transplantation and evaluate the model. Methods The feces of depressed and healthy people in the climacteric period were transplanted into simulated sterile mice. Sixty C57BL/6 mice were divided into blank group, depressed fecal bacteria transplantation (FMT?P) and healthy fecal bacteria transplantation (FMT?H)a groups. The blank group (20 mice) was only fed an ordinary diet. The FMT?P group (20 mice) was pretreated with an antibiotic cocktail, and then the model was established by fecal bacteria transplantation in the depressed population. The FMT?H group (20 mice) was administered the antibiotic cocktail, and then the model was established by fecal bacteria transplantation in the healthy population. Each group was continuously fed for 28 days. The general conditions and behavioral tests of mice were observed by tail suspension and new environment feeding tests, the serum levels dopamine (DA), norepinephrine (NE), 5?hydroxytryptamine (5?HT), and γ?aminobutyric acid (GABA) were determined by ELISA, and colon histopathology was observed by HE staining. Results Compared with the blank control group, the body mass of the FMT?P group was increased slowly, the time of depression was significantly prolonged, the feeding time was significantly decreased, and there were depression symptoms such as decreased activity, disheveled and yellow hair, shedding fur easy to fall off, and mental fatigue. The serum levels of GABA, 5?HT, and DA in FMT?P group the group were significantly lower than those in the blank control group. Microscopically, colonic tissue was disordered, glands enlarged glands were increased, and local inflammatory cells had infiltrated. Conclusions The combination of antibiotic cocktail therapy and fecal bacteria transplantation establishes a humanized mouse model of depression.