Objective To establish a BALB/ c mouse model of total hysterectomy and to investigate and analyze its characteristics and formation mechanism. Methods The control group was fed conventionally without any treatment. The mice in the model group were anesthetized and performed hysterectomy. The animals in the sham-operated group had abdominal cavity opened and only exposing the uterus. The changes of body weight were observed dynamically, and at the end of the fourth weeks. The concentration of serum estradiol was determined and histological structure of the ovaries was examined. Results The general status of all the mice after operation was good without obvious inflammation, and the incision healed completely. There was no significant difference in the body weight before operation among the mice, whereas the weight of model group mice was higher than the control group and sham-operation group at the end of the second, third and forth weeks ( P < 0.05). The estradiol contents of the model group was significantly lower than that in control group and sham operation group ( P < 0.01). The histological structure of ovaries in the control group and sham-operation group was normal, however the model group showed differences, such as irregular shape of the ovaries, changed number of mature follicles, loosely distributed granulosa cells, and apoptosis. Conclusions The mouse model of total hysterectomy established in our study can well simulate the clinical manifestations of ovarian dysfunction after operation, and is an ideal model for the study of complications after ovariectomy and screening of drugs.