Traumatic injuries to peripheral nerves often leave gaps that cannot be repaired by direct suture methods. In such instances, repair with a tubular nerve guide, allows connection of the nerve ends, provides directional guidance, and concentrates endogenous trophic factors for regenerating axons. We hypothesized that collagen nerve guides containing longitudinally oriented channels would further improve the outcome of nerve repair by increasing the surface area available for cell migration. We restored the continuity of a 10mm peripheral nerve gap (rat sciatic nerve) by suturing the nerve stumps into a type I collagen nerve guide (1.5 mm ID), which contained longitudinal channels. Two different channel designs were tested. They were compared to empty nerve guides and autografts. One channel design contained five longitudinally-oriented collagen microtubes (0.4 mm ID) and the other contained 32 longitudinally-oriented collagen filaments (90 micro m diameter). Nerve regeneration was examined at 6 weeks and 12 weeks post repair by a determination of the number and diameter of myelinated axons in the middle sections of the nerve guides. Sciatic function Indices were calculated from walking tracks and static stance images, and electrophysiological assessments were performed. Compound muscle action potentials of the gastrocnemius and intrinsic muscles of the foot were recorded from animals in each group at 12 weeks, indicating that axons regenerated through the nerve repair site, into the distal nerve stump, and successfully reinnervated peripheral targets. At 6 weeks, there was no significant difference between the mean number of myelinated axons with the mid sections of the 3 types of nerve guides (P = 0.488). At 12 weeks, the nerve guide that contained 5 microtubes within its lumen had significantly more axons than the nerve guide that contained 32 filaments in its lumen (P = 0.008). The mean myelinated axon number in the microtube group is larger than the empty nerve guide group but this difference was not statistically significance (P < 0.05). Autografts at both 6 and 12 weeks had significantly more myelinated axons in the mid section of the repair site than either of the nerve guide repairs at the respective time points (P < 0.05).