Neuropeptide Y (NPY) increases feeding by direct action in the central nervous system (CNS). Interleukin-1β (IL-1β), on the other hand, induces anorexia when administered ICV at estimated pathophysiological (e.g., yielded by 1.0 ng/rat dose) and pharmacological (≥4.0 ng) concentrations in the cerebrospinal fluid (CSF). In the present study, we investigated NPY/IL-1β interactions using the ICV administration. ICV microinfusion of NPY (5.0 μg) significantly increased 2-h food intake (by 89%), whereas IL-1β decreased 2-h food intake (32% decrease with 1.0 ng/rat; 53% with 4.0 ng/rat; and 51% with 8.0 ng/rat). NPY (5.0 μg) blocked the anorexic effect induced by all doses of IL-1β when both compounds were administered concomitantly. Central infusion of NPY was also able to induce feeding in IL-1β-pretreated rats exhibiting marked anorexia. The results show that ICV-administered NPY blocks and reverses the anorexia induced by estimated pathophysiological and pharmacological concentrations of IL-1β in rats. A second interpretation of a data subset is that IL-1β attenuates or blocks NPY-induced increase in feeding depending on the IL-1β dose used. Blockage and reversal of IL-1β-induced anorexia by NPY suggest the importance in studying cytokine-peptide interactions in the regulation of feeding behaviour. Understanding these endogenous interactions may produce strategies with potential therapeutic implications for chronic diseases associated with long-term anorexia.