Problem: To investigate whether caloric restriction can modify age-induced intrinsic changes of the skin in Fischer 344 rats. Methods: Fischer 344 rats were procured from the National Institute of Aging and 3 groups of ad libitum (AL) and calorie-restricted (CR)rats were set up for study: young (4 months), adult (1 year), and old (24 months+). Samples of the ventral skin were subjected to histological processing and paraffin microtomy. Readings were obtained in blinded fashion, and standard manual methods of ocular grid morphometry and stereological point counting were applied. The parameters assessed were the number of epidermal nuclei, depth of epidermis, dermis, and adipose layer (μm), and percentage area of dermis occupied by collagen bundles, elastic fibers, pilosebaceous units, and capillaries. Using SPSS 11.0 and Excel statistical software the data were analyzed by 2-factor analysis of variance (general linear model-univariate procedure) to test the null hypotheses about the effects of age, diet, and age-diet interaction effects on the dependent variables, ie, various skin parameters. Results: Both age and diet had significant effects on the epidermal component of the skin. Diet effect was seen in the dermal thickness (F9.26,P.005) with larger values in aging AL animals. Dermal adipose tissue showed pronounced effects of calorie restriction (F5.89,P.021). Elastic and collagen fibers manifested tri-phasic age effect in both nutritional groups with higher values in adult animals. There was no noticeable change in the percentage area of pilosebaceous units. Conclusion: This model shows alterations of skin histomorphology with age, some of which can be modulated with caloric restriction. Significance: Microscopic studies are useful for investigating the effects of chemotherapeutic agents on the skin in suitable age-controlled laboratory animals. The use of CR animals may elucidate whether dietary control can modify the response to such therapies. Support: None reported.