In a group of 14 healthy aged subjects, donkey and goat milk was administered respectively, for a period of one month. Cytokine profile [interleukin (IL)-12, IL-10, IL-1β, IL-8, IL-6 and Tumor Necrosis Factor (TNF)-α] was assessed before and after milk intake by means of a cytometric bead array test. Data demonstrated that IL-12 was undetectable, while IL-10, IL-1β and TNF-β were released in very low amounts. Quite interestingly, IL-8 was increased by donkey milk administration, while same cytokine was dramatically decreased following goat milk intake. Same pattern of response was noted with IL-6 even if levels of these cytokine were lower than those detectable in the case of IL-8. Taken together, these findings indicate that administration of donkey milk in the aged host is able to upregulate the immune response, while goat milk seems to reduce the exaggerated acute phase response in elderly.