OA progression is also influenced by inflammation, which is possibly affected by mechanical stress . Acute inflammation is one of the triggers for OA. Intra-articular injection of mono-iodoacetate (MIA) induces arthritis and 1 mg MIA is often used to induce arthritis in rats. However, in this condition, both cartilage and bone are rapidly destructed [8–10]. Therefore, the use of this amount seems to be inappropriate for analyzing OA progression in OA models. It is still debated whether strenuous running in the inflammatory phase produces beneficial or harmful effect in rat knees (Table 1). We hypothesized that it is possible to reduce the running distance required to make OA in combination with another OA inducer as MIA. If both strenuous running and low amounts of MIA induce OA in an additive manner, this will be a good model for mimicking OA in rats. Secondly, we examined the influences of strenuous running and/or low amounts of MIA injection on cartilage.