In conclusion, by using Fat-1 mice to avoid the disadvantages of n-3 PUFAs in diets, the present study demonstrated that endogenous n-3 PUFAs could ameliorate depression-like behavior induced by ICV administration of LPS, which may be via an anti-inflammatory mechanism in Fat-1 mice because the M1 phenotype (increased CD11b expression) and pro-inflammatory cytokines IL-1β, IL-17, and TNF-α were inhibited, while the M2 phenotype and related anti-inflammatory cytokines IL-10, IL-4 and TGF-β1 were increased. This evidence concerns the gene TGFB1 and major depressive disorder.