Abstract: We studied the effects of quercetin (Q) on the behavioral responses and integral and metabolic indices in male db/db mice genetically predisposed to obesity and C57Bl/6J mice fed a diet with an excessive energy value. We examined forepaw grip strength, exploratory activity, anxiety, and short-term memory, as well as integral and biochemical indices, and the contents of leptin, ghrelin, and IL-10. We found differences between two models of obesity in the integral and biochemical indices and behavioral responses to Q treatment. In the db/db mice, they were associated with knockout of the Lepr gene encoding the leptin receptor, which prevented the neurotropic and regulatory functions of leptin. These effects of Q detected should be considered when justifying the dose and timing of this nutraceutical in clinical practice.