This paper reports the pathologic and functional changes of the sciatic nerve indirectly injured by firearms and its effect on wound healing. Twelve dogs were used. Their hind legs were shot with 1.03-gram steel spheres, avoiding direct injury to the sciatic nerve. The experimental animals were divided into two groups according to the impact velocity, that is, a 1,500 m/sec high velocity projectile (HVP) group and a 400 m/sec, low velocity projectile (LVP) group as a control. After wounding, the same procedure was followed in all dogs. At intervals, the tissues of the wound track were excised to determine the level of cyclic nucleotides (cAMP, cGMP), secondary messengers of neurotransmitters, the activity of acetylcholinesterase (AChE), and the content of hydroxyproline, which indicates the degree of wound healing. The sciatic nerve next to the wound track was excised for light and electron microscopic study. The neurofilament in the sciatic nerve was examined by immunohistochemistry with monoclonal neurofilament-200 antibody. The results showed that the indirect injuries to the sciatic nerves of the HVP group were more severe than in those in the LVP group and included naked axons, stripped myelin sheaths, widened nodes of Ranvier, and decrease in the numbers of neurofilaments. At 6 hours, cAMP content in the HVP group was significantly lower than that in the LVP group. It began to rise and approached to the level of LVP group at 10 days. The cGMP content, activity of AChE, and hydroxyproline content of the HVP group were significantly lower than those of the LVP group. The results suggested that the indirect injury to sciatic nerves, especially to the cytoskeleton, after HVP wounds may induce the disturbance of an axoplasmic flow and influence the metabolism of trophic factors such as cAMP, cGMP, and AChE. All changes could contribute to the delay in wound healing.