Increased interest is being raised on the interaction between systemic inflammation and the brain. The choroid plexus (CP) constitutes a monolayer of epithelial cells located within the brain ventricles and is responsible for the production of cerebrospinal fluid (CSF). Despite the knowledge that the CP capillaries are fenestrated, allowing free passage of molecules and cells, the involvement of the vast blood-brain boundary represented by the CP/CSF barrier in brain inflammatory processes has seldom been considered. In the present study we investigate, in mice, how the expression of genes encoding major constitutively expressed CP proteins is influenced by a systemic inflammatory stimulus. Confirming that the CP responds to peripheral inflammation, the messenger RNA (mRNA) levels of the pro-inflammatory cytokines interleukin 1 beta and tumor necrosis factor alpha are rapidly induced. As for the constitutively expressed proteins, while the mRNA for genes encoding transthyretin and transferrin remain unaltered by the inflammatory challenge, that for prostaglandin D2 synthase (LPTGDS) is up-regulated at 6 h, and stays up-regulated up to 24 h after lipopolysacharide administration. Accordingly, LPTGDS CSF levels are also augmented. LPTGDS catalyzes the synthesis of the major prostanoid of the CNS and, being increased in the CSF, might mediate immune signaling into the brain. These observations emphasize that the CP must be considered a relevant mediator of immune signals between the periphery and the brain.