Major depression is one of the most disabling disorders. Yet, the pathogenesis of this mental disorder is poorly understood. Hippocampus is generally believed to be associated with pathogenesis of depression. In this study, we adopted a proteomic approach to examine possible alterations of protein expression in the hippocampus of a rat depression model. Our results suggest that neurogenesis in hippocampus may play an important role in the pathogenesis of major depression.