In this study we examined fasted and refed cfos activation in cortical, brainstem, and hypothalamic brain regions associated with appetite regulation. We examined a number of time points during refeeding to gain insight into the temporal pattern of neuronal activation and changes in endocrine parameters associated with fasting and refeeding. In response to refeeding, blood glucose and plasma insulin returned to basal levels within 30 minutes, whereas plasma nonesterified fatty acids and leptin returned to basal levels after 1 and 2 hours, respectively. Within the hypothalamic arcuate nucleus (ARC), fasting increased cfos activation in ∼25% of neuropeptide Y neurons, which was terminated 1 hour after refeeding. Fasting had no effect on cfos activation in pro-opiomelanocortin neurons; however, 1 and 2 hours of refeeding significantly activated ∼20% of ARC pro-opiomelanocortin neurons. Acute refeeding (30, 60, and 120 minutes), but not fasting, increased cfos activation in the nucleus accumbens, the cingulate cortex (but not the insular cortex), the medial and lateral parabrachial nucleus, the nucleus of the solitary tract, the area postrema, the dorsal raphe, and the ventromedial nucleus of the hypothalamus. After 6 hours of refeeding, cfos activity was reduced in the majority of these regions compared with that at earlier time points. Our data indicate that acute refeeding, rather than long-term fasting, activates cortical, brainstem, and hypothalamic neural circuits associated with appetite regulation and reward processing. Although the hypothalamic ARC remains a critical sensory node detecting changes in the metabolic state and feedback during fasting and acute refeeding, our results also reveal the temporal pattern in cfos activation in cortical and brainstem areas implicated in the control of appetite and body weight regulation.