Polygala japonica Houtt. (PJ) has been reported have positive effect on the nerves system including depression, but the underlying mechanism is needed to be understood. Here we show that PJ counteracts behavioral effects induced by chronic restraint, a model of depression mimicking exposure to stress, through adult hippocampal neurogenesis (AHN) enhancement. Chronic stress increased the immobility time in the tail suspension test (TST) and forced swim test (FST) and decreased the time in the center of elevated plus maze (EPM) relative to controls. Moreover, chronic stress also induced the cognitive deficit in novel object recognition test, object location test and barnes maze. These behavioral alterations were accompanied by the decreased AHN. Treatment with PJ reversed the behavioral and AHN alterations. We also found that PJ had no significant effect on cell proliferation and neuronal differentiation in dentate gyrus (DG) of the hippocampus, but it inhibited the apoptosis of the newborn neurons by activation of bcl-2 and phopho-erk1/2 and increased the number of the newborn neurons. Our results demonstrate that administration of PJ to chronic stress mice alleviates depression-like behaviors and normalizes the deficit in hippocampal neurogenesis with inhibiting newborn neuron apoptosis.