Visfatin, also known as pre-B cell colony enhancing factor (PBEF) or nicotinamide phosphoribosyltransferase (NAMPT), is a cytokine that is produced by adipose tissue, skeletal muscle, liver and immune cells. We studied the effects of visfatin/PBEF/NAMPT on feeding behavior, hypothalamic steady state concentrations of aminergic neurotransmitters and hypothalamic mRNA levels of anorexigenic peptides, such as cocaine- and amphetamine-regulated transcript (CART) peptide, corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), and orexigenic peptides, such as agouti-related peptide (AgRP) and neuropeptide Y (NPY). Forty-eight rats were injected in the arcuate nucleus (ARC) of the hypothalamus with either saline or visfatin/PBEF/NAMPT (3 microg). Food intake was recorded 1, 2 and 24 h following injection, and either dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytryptamine, 5-HT) or peptide gene expression were evaluated 2 and 24 h after visfatin/PBEF/NAMPT administration. Compared to vehicle, visfatin/PBEF/NAMPT significantly increased food intake, as evaluated 1, 2 and 24 h post-injection. Visfatin/PBEF/NAMPT treatment led to a significant decrease of DA steady state concentration, CART and CRH mRNA levels. Consequently, visfatin/PBEF/NAMPT could play an orexigenic role in the ARC, and the effect could be mediated by modulation of DA, CART and CRH activity in the hypothalamus.