The hypothalamus controls food behavior, and the abnormalities in this regulation induce obesity. This is largely due to the changes in the balance of the hypothalamic factors, such as ore-xigenic factors, including orexin (OR), agouti-like peptide (AgRP) and neuropeptide Y (NPY), and anorexigenic factors including the melanocortin peptides generated from pro-opiomelanocortin (POMC). The data on the expression and the ratio of these factors in obesity induced by the high-calorie diet are few and contradictory. The aim was to study the expression of POMC, OR of the A-type (OR-A), AgRP and NPY in the hypothalamic structures of male rats with cafeteria diet-induced obesity as compared to control animals. Starting the 26-day-old age, the rats consumed a cafeteria diet for 12 weeks, which leads to obesity, insulin resistance, the changes in the carbohydrate and lipid metabolism, and hyperleptinemia. In the perifornical area of the hypothalamus of obese rats, a significant decrease in the number of OR-A and the mRNA expression for the gene encoding pre-proorexin, the OR-A precursor, was shown. In the hypothalamic arcuate nuclei of obese rats, the expression of the gene for AgRP, the antagonist of type 4 melanocortin receptor, was decreased, the expression of the gene for POMC was increased, and the expression of the gene for NPY changed to a small extent. Thus, in different areas of the hypothalamus of rats with cafeteria diet-induced obesity, the compensatory processes are triggered to increase anorexigenic effects and suppress orexigenic effects, which should weaken hyperphagia and prevent the negative metabolic and hormonal changes caused by excessive caloric intake