A reduction in food intake is commonly observed after bacterial infection, a phenomenon that can be reproduced by peripheral administration of Gram-negative bacterial lipopolysaccharide (LPS) or interleukin-1beta (IL-1β), a pro-inflammatory cytokine released by LPS-activated macrophages. The arcuate nucleus of the hypothalamus (ARH) plays a major role in food intake regulation and expresses IL-1 type 1 receptor (IL-1R1) mRNA. In the present work, we tested the hypothesis that IL-1R1 expressing cells in the ARH mediate IL-1β and/or LPS-induced hypophagia in the rat. To do so, we developed an IL-1β-saporin conjugate, which eliminated IL-R1-expressing neurons in the hippocampus, and micro-injected it into the ARH prior to systemic IL-1β and LPS administration. ARH IL-1β-saporin injection resulted in loss of neuropeptide Y-containing cells and attenuated hypophagia and weight loss after intraperitoneal IL-1β, but not LPS, administration. In conclusion, the present study shows that ARH NPY-containing neurons express functional IL-1R1s that mediate peripheral IL-1β-, but not LPS-, induced hypophagia. Our present and previous findings indicate that the reduction of food intake after IL-1β and LPS are mediated by different neural pathways.