Objectives : We aimed to identify the antidepressant effect of liver tonification acupuncture treatment (ACU (LT); KI10, LR8, LU8, LR4) and four gate acupuncture treatment (ACU (FG); LI4, LR3) and its brain neural activity in the normal and chronic restraint stress (CRS)-induced mouse model. Methods : Firstly, normal mice were given ACU (LT) or ACU (FG) and the c-Fos expressions in each brain region were analyzed to examine brain neural activity. Secondly, CRS was administered to mice for 4 weeks, then ACU (LT) or ACU (FG) was performed for 2 weeks. The depression-like behavior was evaluated using open field test (OFT) before and after acupuncture treatment. Then, the c-Fos expressions in each brain region were analyzed to examine brain neural activity. Results : In normal mice, ACU (FG) regulated brain neural activities in the hypothalamus, hippocampus, and periaqueductal gray. ACU (LT) changed more brain regions in the prefrontal cortex, insular cortex, striatum, and hippocampus, including those altered by ACU (FG). In CRS-induced model, ACU (LT) alleviated depression-like behavior more than ACU (FG). Also, brain neural activities in the motor cortex area 2 (M2), agranular ventral part and piriform of insular cortex (AIV and Pir), and cornu ammonis (CA) 1 and CA3 of hippocampus were changed by ACU (LT), and those of AIV and CA3 were also changed by ACU (FG). As in normal mice, ACU (LT) resulted in changes in more brain regions, including those altered by ACU (FG) in CRS model. M2, Pir, and CA1 were only changed by ACU (LT) in depression model, suggesting that these brain regions reflect the specific effect of ACU (LT). Conclusions : ACU (LT) relieved depression-like behavior more than ACU (FG), and this acupuncture effect was associated with modulation of brain neural activities in the motor cortex, insular cortex, and hippocampus.