Systemic inflammation occurring in premature babies is a risk factor for neurological sequelae. However, the mechanisms underlying how systemic inflammation is transmitted to intracranial tissues and brains remain to be clarified. The Pathology Research Team at the Faculty of Health Sciences of Kyorin University is studying how intracranial tissues and cells are involved in immune responses to systemic inflammation using mouse models. In this study, we investigated which parts of the intracranial tissues contain macrophages/microglia that express interleukin (IL) -1β in response to intraperitoneal endotoxin injection into newborn mice. One-day-old C57BL/6N mice were treated with a single intraperitoneal injection of lipopolysaccharide (LPS) derived from Escherichia coli O55:B5 for the experimental groups. The other mice in the control group were treated with saline injection. One and four hours after injection, the mice were decapitated, and the heads were immersed in Zamboni’s fixative. Histological sections were then cut using a cryostat from the frozen blocks of the cranial tissues containing the calvaria and brain. Double immunofluorescence staining was performed using F4/80 as a marker for macrophages/microglia and IL-1β as an index of the immune response. Areas of interest (AOIs) were set in the choroid plexus, cephalic mesenchyme, and brain parenchyma. In each AOI, the numbers of F4/80-immunopositive cells and cells double-immunopositive for F4/80 and IL-1β were counted. The proportion of IL-1β-immunopositive cells was calculated by dividing the number of cells double-immunopositive for F4/80 and IL-1β by the number of all F4/80-immunopositive cells. The proportion of IL-1β-immunopositive cells was 64.3% in the choroid plexus and 6.5% in the cephalic mesenchyme of mice 4 h after LPS injection. The proportion of IL-1β-immunopositive cells did not increase significantly in the brain parenchyma. Therefore, in 1-day-old mice, the macrophages of the choroid plexus and cephalic mesenchyme constituted the initial immune reaction in response to systemic inflammation, whereas the microglia of the brain parenchyma did not contribute to the initial immune response to systemic inflammation. This study was performed with financial support from the Intramural Grants Program “Health Sciences Collaborative Research Promotion Project”, in which the authors were awarded a grant in fiscal year 2021.