The neurobiology of sex differences in response to chronic stress is a topic that has been extensively discussed in the scientific literature, but remains poorly understood. In our research, we found that chronic unpredictable mild stress (CUMS) experienced during adolescence induces different behavioural patterns in adult males и females. Similarly, immunohistochemical analysis of the CA1 field of the dorsal and ventral hippocampus revealed no changes in quantitative and morphological changes in astrocytes at long-term period after CUMS. Real-time PCR analysis showed no increase in SIGMAR1 expression level relative to individual housekeeping genes after CUMS. Analysis of mouse cerebral cortex homogenates showed that IL-1β levels decreased after stress modelling only in males. However, Sigma R1 levels were significantly higher in the CUMS group than in the controls in both sexes. It can be concluded that biological sex and age do indeed influence the response to CUMS, although not in all cases. There is a need for further research in order to understand the effects of chronic stress on males and females. This is of crucial importance because men and women are exposed to different risks in relation to stress and mental health.