Taken together, our study revealed that quercetin could alleviate LPS-induced depression like behaviors and impairment of learning and memory in rats, the mechanism of which might be partly associated with its ability in regulating the BDNF-related imbalance expression of Copine 6 and TREM1/2 in the hippocampus and PFC. The gene discussed is TREM1; the disease is major depressive disorder.