In the pathogenesis of central nervous system (CNS) disorders, an increasingly important role is attributed recently to unhealthy lifestyle, which consists primarily of a high caloric diet (i.e., western), chronic exposure to stress, and lack of physical activity. However, the mechanisms responsible for energy metabolism impairment induced by unhealthy lifestyles compromising CNS functions are poorly understood. Research on the effects of physical activity on the CNS is especially important, because it may result in the development of new methods of therapy inspired by natural protective mechanisms. In our study we employed a new and rarely used approach – a forced running wheel. The lack of electrical stimulus in the aforementioned system successfully makes a breakthrough in the study of animal physical activity. Physiological and behavioral responses of the organism to stress are closely related to sex. Epidemiological studies indicate that women are more vulnerable to the adverse effects of stress and despite that, most of the experimental studies are conveyed on male animals. The investigations were carried on female rats. The main goal of our study was to verify the hypothesis that regular exercise may reduce the disturbances induced by lifestyle modifications, like western diet and/or stress exposure. Adult female rats were fed with the prepared chow reproducing the human western diet and/or subjected to a stress induced by social instability. This stress protocol is characterized by a low degree of invasiveness. To evaluate if regular physical activity may reduce the adverse effects caused by diet and stress, female rats were additionally subjected to the procedure of forced physical activity. A proteomic analysis was conducted on samples obtained from the frontal cortex – a region that plays an important role in cognitive processes as well as is involved in the mechanisms engaged in the response to stress.