The proinflammatory cytokine interleukin-1b (IL-1b) influences neuroendocrine activity and produces others effects, including fever and behavioral changes such as anxiety.The melanocortin neuropeptides, such as alpha melanocyte-stimulating hormone (a-MSH), antagonize many actions of IL-1, through specific melanocortin receptors in central nervous system. The objective of the present study was to establish the effect of MSH peptides on IL-1b-induced anxiety-like behavior and the type of melanocortin receptors involved. We evaluated the effects of intracerebroventricular (i.c.v.) administration of IL-1b (30 ng) and melanocortins receptors agonists: a-MSH, a MC3/MC4-R agonist (0,2 mg) and g-MSH a MC3-R agonist (2 mg) or HS014, a MC4-R antagonist ( 2 mg ), on elevated plus-maze test. Injection of IL-1b induced an axiogenic-like response, as indicated by reduced open arms entries and time spent on open arms. The administration of a-MSH reversed IL-1b-induced anxiety. Coadministration of HS014 inhibited the effect of a-MSH. However, the associated treatment with g-MSH did not affect the anxiety response to IL-1b. These data suggest that a-MSH, through central MC4-R can modulate the anxiety-like behavior induced by IL-1b.