In LPS-induced depression-like mice model, a single dose of ketamine can improve depression-like behaviors and inhibit release of pro-inflammatory cytokines (IL-1α, IL-6, Eotaxin, G-CSF, MIP1b, and TNF-α) in the brain, attenuate morphological microglia reactivity and cytotoxic microglia polarization, reverse the overexpression of heme oxygenase 1 transcripts, and reduce the production of quin in microglia. This evidence concerns the gene HMOX1 and major depressive disorder.