In summary, paeoniflorin could alleviate the depression of rats with CUMS and ameliorate the pathological injury of nerve cells in the hippocampus, indicating that the antidepressant effect and protective effect of paeoniflorin on hippocampal nerve cells might be mediated by ERK-CREB signaling pathway, which are the downstream pathway of BDNF. Here, BDNF is linked to major depressive disorder.