〔Abstract〕 Objective To investigate the effects of estrogen deficiency on depression-like behavior and mitochondrial function in hippocampus, and to study the underlying mechanisms. Methods The female adult C57BL/6 mice were randomly assigned to Sham group, Ovx group and Ovx+E2group. On the 7th day after operation, Ovx+E2group was subcutaneously injected with 17β-estradiol(E2) for 4 weeks. Then another 48 female adult C57BL/6 mice were randomly divided into Sham group, Sham+MnTBAP group, Ovx group and Ovx+MnTBAP group. After operation for one week, MnTBAP was injected into the hippocampus of mice in Sham+MnTBAP group and Ovx+MnTBAP group. The depression-like behaviors of the mice were monitored by sucrose preference test and forced swimming test. Then the mice were decapitated, and the hippocampus samples were collected. Mitochondria of hippocampus were isolated using mitochondria fractionation kit. The concentrations of adenosine triphosphate(ATP), reactive oxygen species(ROS) and mitochondrial membrane potential were determined, respectively. Results Compared with Sham mice, Ovx showed a decrease in the percentage of sucrose consumption, an increase in immobility time and the alterations of hippocampal mitochondrial function, which were reversed by estrogen treatment. Intrahippocampal injection of MnTBAP significantly increased the percentage of sucrose consumption and decreased immobility time in Ovx mice. Conclusion Hippocampal mitochondrial dysfunction contributes to estrogen deficiency-induced depression-like behaviors.