Depending on intensity, eccentric exercise is experimentally and clinically documented to have opposing dual effects on skeletal muscle; intense eccentric exercise damages muscle, but daily low-load eccentric exercise prevents damage. To clarify the mechanisms of this dual effect, microscopic damage and oxidative stress were studied in rat quadriceps muscle. Oxidative stress was estimated from an immunostaining of advanced glycation end-products (AGE) and a measurement of muscle tissue preparations, the ability to scavenge reactive oxygen species (ROS). Intense eccentric downhill running (IEE) induced muscle damage that was, microscopically apparent 3 days later. Since AGE-positive cells and decreased ROS scavenging activity were observed earlier (on the day after IEE), cellular damage may be related to ROS production. Intense concentric uphill running (ICE) induced an immediate but transient decrease in ROS scavenging activity, which recovered within a day. Neither AGE-positive cells nor microscopic damage was observed after ICE. Since each contracting muscle fiber develops greater tension during eccentric rather than concentric exercise, the initial trigger of IEE-induced muscle damage may be damage to muscle fibers and connective tissues at the subcellular level. Daily low-load training of eccentric downhill running (LET), but not concentric uphill running, efficiently prevented muscle damage after subsequent IEE. No evident elevation of ROS scavenging activity was evident after LET. We concluded that LET prevents IEE-induced muscle damage not through elevated ROS scavenging activity, but through a suppression of initial subcellular damage that triggers subsequent ROS-producing processes, resulting in cellular delayed damage.