Immunosenescence is characterized by a progressive decline of immune functions with age and both innate and adaptive immune responses are severely impaired and increase the susceptibility of old people to infections, tumors, and autoimmune diseases. Nutrition seems to be fundamental in the mechanism of immune recovery in the elderly. A series of reports have emphasized the beneficial effects of donkey milk in the immunocompromised host for the inhibition of bacterial activity and the prevention of atherosclerosis because of its antioxidant properties. The aim of the study was the evaluation of pro-inflammatory and anti-inflammatory effect of donkey milk in aged individuals. In a group of 14 healthy aged subjects, donkey milk was administered 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-α was released in very low amounts. IL-8 was increased by donkey milk administration. The same pattern of response was noted with IL-6. These findings indicate that the administration of donkey milk in the aged host is able to upregulate the acute immune response.