We examined cytokines in rat median nerves following performance of a high repetition reaching and grasping task at a rate of 8 reaches/min for up to 8 weeks. IL-1alpha, IL-1beta, TNF-alpha, IL-6 and IL-10 were analyzed by immunohistochemistry. Double-labeling immunohistochemistry for ED1, a marker of phagocytic macrophages, was also performed. We found increased immunoexpression of IL-6 by week 3, increases in all 5 cytokines by week 5. This response was transient as all cytokines returned to control levels by 8 weeks of performance of a high repetition negligible force task. Cytokine sources included Schwann cells, fibroblasts and phagocytic macrophages (ED1-immunopositive). These findings suggest that cytokines are involved in the pathophysiology of repetitive motion injuries in peripheral nerves.