Background and aims: Moderate physical exercise and dietary restriction have both been demonstrated to delay some of the adverse effects of aging. In order to elucidate similarities or dissimilarities in their mode of action on the aging immune system in a comparative setting, we examined significant parameters of cell-mediated immunity in Sprague- Dawley rats. Methods: Male Sprague-Dawley rats, housed individually, were divided into four groups, living from 5 months (baseline group BL) up to 15, 19 and 23 months of age as follows: voluntary running in wheels (RW), food restricted by feeding to pair weight with RW animals (PW), forced running on treadmills (TM), and sedentary controls with ad libitum access to food (S1). White blood cell counts, capacity for lymphocyte proliferation in response to Concanavalin A, and interleukin-2 (IL-2) plasma concentrations were determined. Results: White blood cell counts and the cell numbers of lymphocytes, neutrophil and eosinophil granulocytes were significantly lower in the older RW and PW groups. We observed influences of forced exercise on lymphocyte proliferation: blastogenic reactivity was higher in TM animals compared with RW and PW animals at 23 months of age. Exclusively for RW animals, we found lower plasma concentrations of IL-2 at 23 months. Conclusions: Our data support the idea that moderate physical exercise modulates age-associated decline in the cell-mediated immunity of old Sprague-Dawley rats significantly more than corresponding dietary restrictions.