This study was committed to making a comprehensive investigation of Changyu Daotan Decoction's efficacy in the depression mice model, and it turned out that the Changyu Daotan Decoction was capable of restoring the hippocampus of the depression mice and altering the expressions of neurotrophic factors (the expressions of β-Catenin, cyclin D1 and in GSK-3β BDNF, GFAP, NGF, and Wnt signaling pathways). Here, GFAP is linked to major depressive disorder.