Part I of this review addressed the possible modulatory role of exercise on neuronal growth factors to promote brain health in neurodegenerative diseases such as multiple sclerosis (MS), which is characterized by varied patterns of inflammation, demyelination and axonal loss. Part II presents evidence that supports the potential neuroprotective effect of exercise on the modulation of immune factors and stress hormones in MS. Many current therapies used to attenuate MS progression are mediated, at least in part, through alterations in the relative concentrations of pro- and anti-inflammatory cytokines. Exercise-induced alterations in local and systemic cytokine production may also benefit immune function in health and disease. Exercise immunomodulation appears to be mediated by a complex interaction of hormones, cytokines and neural factors that may favorably influence immune variables in MS. The promising interplay between exercise and brain health in MS deserves further investigation.