Involution of the thymus is one of the most expressed indices of aging of the immune system. The mechanisms of involution of the thymus are relatively well studied, whereas the reasons and mechanisms of accelerated involution of the thymus are less known. We have previously reported that premature aging in OXYS rats is associated with accelerated involution of the thymus. The aim of the present study was to examine morphofunctional conditions of epithelial cells in the thymus of OXYS rats. Immunohistochemical study revealed that in 3.5-month-old OXYS rats, i.e. in the initial period of age-related involution, the network of epithelial cells in the thymus was reduced, and the volume and area of the surface of epithelial cells in the cortical substance was lower compared to control Wistar rats. Electron microscopy found strong changes in the ultrastructure of epithelial cells, such as shrinkage of the cytoplasm volume, a clear decrease in the size and number of secretory vacuoles, and multiple autophagosomes and phagolysosomes. Our data show that a possible mechanism of the reduction of the epithelial network in the thymus of OXYS rats is an enhancement of autophagy, probably related to specific mitochondria dysfunction in these rats. The fact of age-related retardation of autophagy in some tissues is well known. In spite to this, based on the data from OXYS rats, we suppose that long-term deviation of intensity of this process from the physiological level may be directed not only to its attenuation but also to its activation and thus results in degenerative modifications of organs and the formation of the progeroid phenotype of the body.