Normal aging is associated with low-grade neuroinflammation that results from age-related priming of microglial cells. Further, aging alters the response to several anti-inflammatory factors, including interleukin-4 (IL-4). One intervention that has been shown to modulate microglia activation in the aged brain, both basally and following an immune challenge, is exercise. However, whether engaging in exercise can improve responsiveness to anti-inflammatory cytokines is presently unknown. The current study evaluated whether prior exercise training increases sensitivity to anti-inflammatory cytokines that promote the M2 (alternative) microglia phenotype in adult (5-month-old) and aged (23-month-old) C57BL6/J mice. After 8 weeks of exercise or control housing, mice received bilateral hippocampal injections of an IL-4/IL-13 cocktail or vehicle. Twenty-four hours later hippocampal samples were collected and analyzed for expression of genes associated with the M1 and M2 microglia phenotypes. Preliminary results show that IL-4/IL-13 increased expression of the M2 associated genes arginase, Fizz-1, YM1, and CD206. With the exception of CD206, age and/or exercise modulated expression of all M2 associated genes following IL-4/IL-13 administration. Further, aged mice showed increased expression of interleukin-1 β relative to adults, which was unaffected by IL-4/IL-13 or wheel running. Analysis of additional M1 and M2 associated genes is currently in progress. Collectively, preliminary findings indicate that aged mice show a differential response to anti-inflammatory cytokines relative to adult mice and that exercise can modulate aspects of this response.