While inflammation is a natural process, chronic or excessive inflammation in the brain can be harmful. After administration of neuroinflammatory compounds such as lipopolysaccharide (LPS), its signals reach the brain through three main pathways: (1) humoral pathway, (2) afferent vagal pathway, and (3) spinal neuronal pathway. This study aims to gain new insights into mechanisms underlying inflammation-induced brain activation. Neuronal activity is evaluated by c-Fos immunostaining in the LPS-induced inflammation states. LPS activated neurons in the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), insular cortex (IC), hypothalamic paraventricular nucleus (PVN), basolateral amygdala (BLA), thalamic paraventricular nucleus (PVT), hippocampus ventral CA1 (vCA1), locus coerules (LC) and nucleus tractus solitarius (NTS). The activation of the ACC, IC, PVN, and BLA was blocked by intracerebroventricular injection of alloxan, a toxic material to destroy ependymal cells around the ventricle, while the activation of the mPFC, ACC, vCA1, LC, and NTS was blocked by vagotomy. These results suggest that ACC, IC, PVN, and BLA may transmit peripheral inflammatory signals to the brain via the humoral pathway, while mPFC, ACC, vCA1, LC, and NTS transmit signals via the afferent vagal pathway.