Activation of nuclear factor (NF) kappaB and mitogen-activated protein kinase (MAPK) pathways in skeletal muscle has been shown to enhance the gene expression of several enzymes that play an important role in maintaining oxidant-antioxidant homeostasis, such as mitochondrial superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS). While an acute bout of exercise activates NF kappaB and MAPK signaling and upregulates MnSOD and iNOS, administration of chemical agents that suppress reactive oxygen species (ROS) production can cause attenuation of exercise-induced MnSOD and iNOS expression. Thus, ROS generation during exercise may have duel effects: the infliction of oxidative stress and damage, and the stimulation of adaptive responses favoring long-term protection. This scenario explains why animals and humans involved in exercise training have demonstrated increased resistance to oxidative damage under a wide range of physiological and pathological stresses.