Immunohistochemical analysis of the inflammatory cells and complement C3 in the rat skeletal muscle was performed chronologically in bupivacaine-induced myonecrosis. At 30 minutes after injection, polymorphonuclear leukocytes appeared and increased in number, with a peak value at 12 hours, while macrophages reached the highest level at 2 days. In contrast, T cells comprised only a small population. Two weeks after the injection, all types of the inflammatory cells returned to the normal level. Deposition of complement C3 was recognized at 60 minutes at the surface membrane of degenerating muscle fiber. Our observation suggests the importance of both polymorphonuclear leukocytes and complement C3 in the early stage, and macrophages in the later stage of bupivacaine-induced myonecrosis. In addition, our findings cast doubt on the pathological significance of T cells in this model.