Activation of mu opioid receptors makes animals hyperphagic and increase their preference for a high fat diet. Previous studies have suggested that this receptor population plays a role in mediating the hyperphagia that is associated with food deprivation. In this paper, we tested the hypothesis that food deprivation will increase the expression of mu opioid receptors in the ventral medial hypothalamus and arcuate nucleus (VMH/ARC). Food deprivation resulted in a significant increase in the mRNA expression of mu opioid receptors in the VMH/ARC and the lateral hypothalamus (LH) after 48 hours of fasting, but not after 24 hours of fasting, or 12 hours of fasting in either the light or dark. We did not observe a change in the mRNA expression of kappa opioid receptors or delta opioid receptors after food deprivation. When food deprived animals were given a choice between a low fat diet and a high fat diet, they were hyperphagic and consumed significantly more of the high fat diet. When the mu opioid receptors were blocked with beta-funaltrexamine (selective mu opioid receptor antagonist), prior to giving food deprived animals access to both a low fat and high fat diet, it significantly decreased the percentage of high fat diet consumed. These data demonstrate that hypothalamic mu opioid receptors may contribute to the hyperphagia and increased preference for a high fat diet that is associated with food deprivation.