Abstract Proopiomelanocortin (POMC) is a 36kDa glycoprotein implicated in homeostatic balance. We used in situ hybridization histochemistry coupled with quantitative autoradiography to determine the anatomical distribution of POMC mRNA-expressing neurons in the arcuate nucleus (AN) and to examine the effects of prolonged dehydration on POMC gene expression in a semi-desert rodent, Meriones shawi (Shaw’s Jird). In the hypothalamus of control animals, POMC mRNA-expressing neurons were exclusively localized in the AN and they showed a differential distribution and density along its rostro-caudal subdivisions. In dehydrated animals, water deprivation caused a decrease in POMC mRNA labeling in the AN. These results suggest that dehydration stress can induce negative regulation of POMC gene expression in this species. A comparative study of weight variation between control and dehydrated animals showed a weight loss followed by stabilization of weight during prolonged dehydration.