In the present study, the findings indicated that exposure to CRS procedures obviously activated the hippocampal microglia and elevated the expression of TLR4, MyD88, TRAF6, NF-κB p65, TNF-α, and mRNA expression levels of TLR4 in the hippocampus, increased IL-1β, and decreased IL-10 in serum when compared to that of the control group, suggesting the involvement of the stress-induced activation of neuroinflammation in the pathogenesis of depression. This evidence concerns the gene TLR4 and depressive disorder.