The C-Fos gene is expressed immediately following neurons activation. In this study, we performed immunofluorescence for recognition of C-Fos gene expression sites in whole mice brain. The lipopolysaccharide (LPS) is a Gram-negative bacterium its infection causes acute inflammatory reactions accompanied with fever. We injected LPS intraperitoneally (i.p.) in mice and we recognized C-FOS expression at 1, 3, and 6 hours following LPS injection. Our result indicated that PVA, PVH, DM, and DR were the main sites showed C-Fos gene expression at 1 hour following Lps injection. Afterward, at 3 hours following LPS injection C-Fos gene expressed in circumventricular organs (OVLT, SFO, and AP). As well as, it expressed in MPA, Sch, VMH, and ARC. At 6 hour following Lps injection C-Fos gene expression increased in all the previously mentioned nuclei. It was found that some of C-Fos expressing neurons at DR were serotoninergic neurons. Our results give important insights for brain nuclei activated at acute inflammatory conditions accompanied with LPS injection.