The hypothalamic arcuate nucleus is an important target for metabolic and hormonal signals controlling food intake. As demonstrated by c-Fos studies, arcuate neurons are activated in food deprived mice, while refeeding reverses the fasting-induced activation. To evaluate whether an increase in blood glucose has an inhibitory effect on these neurons, we analyzed the c-Fos response to an intraperitoneal glucose injection in fasted mice. This treatment increased blood glucose levels twofold and reduced 2h food intake. Similar to refeeding, it also reversed the fasting-induced activation in the arcuate nucleus. Therefore, an increase in blood glucose might be an important feeding-related signal acting via the arcuate nucleus to oppose orexigenic stimuli.