The aim of this study was to compare the effect of silver salt and silver nanoparticles on the morphofunctional state of the hypothalamic-adrenal system in obese rats. The experiment was carried out on 24 male rats at the age of 6 months. The rats of the control group received standard food. In other groups of animals, obesity was induced using a diet-induced model of metabolic disorders. The rats, modeled for obesity, were divided into several groups. Animals of different groups received NaCl solution, silver nitrate solution and silver nanoparticle solution for 10 days, respectively. After the end of the experiment, the hypothalamic nuclei and adrenal glands, prepared according to the appropriate histological methods, were taken from the animals. In the paraventricular nucleus of the hypothalamus, a small-cell area of neurons was examined. In the adrenal glands of rats, cells of three zones of the cortex were examined: glomerular, fascicular, and reticular. The results of the study showed that obesity led to the increase of functional activity in the nuclei of neurons in the small-cell region of the PVN of the rat hypothalamus. The cells of the glomerular zone of the adrenal cortex had the maximum increase in functional activity, the fascicular zone – a moderate increase in functional activity, and no significant changes were recorded in the reticular zone. It was shown that the silver salt solution caused the increase in the functional activity of PVN neurons in the hypothalamus of obese rats. In the glomerular zone, the parameters of the functional activity of cells increased significantly, in the fascicular zone, the parameters of cell nuclei decreased to the greater extent, in the reticular zone, mainly the parameters of the nuclei increased. It was investigated that the solution of silver nanoparticles caused the intensification of PVN cells in the hypothalamus of obese rats. In the glomerular zone of the adrenal cortex, a significant increase in cell parameters was observed, in the fascicular zone – the increase in the cytoplasm parameters, in the reticular zone – the decrease mainly in the parameters of cell nuclei. In general, the administration of the solution of silver nanoparticles led to more pronounced activation of PVN cells of the hypothalamus and adrenal cortex in obese rats than the silver salt.