Social requirements are needed for living in an aging society and the individual longevity. Among them, improved health and medical cares, which are appropriate for aging society are strongly demanded. Human cord blood-derived plasma (hUCP) has recently emerged for its unique anti-aging effects. In the present study, we investigated brain rejuvenation, particularly olfactory function, which could be achieved by a systemic administration of young blood and its underlying mechanisms. Over 24-month-old mice were used as an aged group and administered with intravenous injection of hUCP repetitively, for 8 times. Anti-aging effect of hUCP on olfactory function was evaluated by buried food finding test. To investigate the mode of action of hUCP, brain, serum and spleen of mice were collected for further ex vivo analyses. Systemic injection of hUCP improved aging-associated olfactory deficits, reducing the time for finding food. In the brain, although an infiltration of activated microglia and its expression of cathepsin S were remarkably decreased, any significant changes of proinflammatory factors were not detected. On the other hand, peripheral immune balance distinctly switched from predominance of Th1 to alternative regulatory T (Treg). These findings indicate that systemic administration of hUCP attenuates age-related neuroinflammation and subsequent olfactory dysfunction by modulating the peripheral immune balance toward Treg cells, suggesting another therapeutic function and mechanism of hUCP administration.