Objectives.Active inflammatory responses play an important role in the pathogenesis of depression.We hypothesized that the rapid antidepressant effect of ketamine is associated with the down-regulation of pro-inflammatory mediators.Methods.Forty-eight rats were equally randomized into six groups (a control and five chronic unpredictable mild stress (CUMS) groups) that received either saline or ketamine, respectively.The forced swimming test was performed, and the hippocampus was subsequently harvested for determinnation.Levels of IL-1β, IL-6, TNF-α,indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), and tryptophan (TRP) were measured.Results.CUMS induced depression-like behaviour and up-regulated levels of IL-1β, IL-6, TNF-α, IDO, and the KYN/TRP ratio, which was partially antagonised by ketamine.Conclusion.Depression is associated with increased inflammatory mediators and ketamine's antidepressant effect is associated with the down-regulation of pro-inflammatory cytokines.