Background: Technology-induced increases in stress can have adverse effects on the nervous system. Objectives: The aim of the present study was to investigate the effects of chronic multiple stressors on morphometric changes in Betz cells in the rat cerebral cortex. Methods: Eighteen Wistar rats were divided randomly into two equal groups. One group was then exposed to different types of stress (forced swimming, restraint, water deprivation, isolation, and food deprivation) for 10 days, and the other group (control) remained in cages and was not exposed to any stress. The animals were then weighed and anesthetized, and their brains were removed and weighed. After fixation, the brain samples were prepared for light microscopy study. The number, size, and incidence of apoptosis of Betz cells in the internal pyramidal layer were determined using the ImageTool software program, and the data were analyzed using SPSS software and a t-test, with a value of P < 0.05 considered statistically significant. Results:The mean number and size of Betz cells in the stressed group decreased significantly compared to those in the control group (P < 0.05). Qualitative observations revealed chromatolysis of Nissl bodies, nucleus condensation, and a decrease in neural processes. The mean number of apoptotic cells in the stressed group were also significantly increased compared to that of the control group (P < 0.001). Conclusions:The results showed that chronic multiple sequential stress can have negative effects on the cerebral cortex of rats by reducing the size and number of Betz cells and increasing the incidence of apoptosis. More studies are needed to confirm these results.