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Objective To investigate the role of porcine small intestinal submucosa (SIS) conduit in axonal regeneration of rat sciatic nerve with a 10 mm gap. Methods Forty-eight rats were randomly divided into three groups (n=16). Following a 10 mm gap was made in one side of the sciatic nerve of each rat; previously prepared SIS and auto-nerve graft were interposed into the gap to reconnect the proximal and distal ends of the nerve, respectively. In the control group, the nerve gap remained unconnected. The samples of the SIS, graft, and distal nerve in group 1 and group 2 were harvested at 6 weeks and 10 weeks after operation, respectively. Axonal regeneration was evaluated by histology, electrophysiology, and quantitated by using computer-analyzed image.Results Regenerative nerve fibers were evident which contained much myelinated axons and grew over the gap in the SIS conduits at 10 weeks. Electrophysiological examination and computer-analyzed image showed that axonal regeneration in the SIS group was similar to that in the auto-nerve grafting group at 10 weeks. Conclusion SIS as a conduit possesses the ability for axonal regeneration of the peripheral nerve, thereby having a potential to be an alternative bio-material instead of the autograft to repair the peripheral nerve gap.