Regeneration of endogenous axons through a Schwann cell (SC)-seeded scaffold implant has been demonstrated in the transected rat spinal cord. The formation of a cellular lining in the scaffold channel may limit the degree of axonal regeneration. Spinal cords of adult rats were transected and implanted with the SC-loaded polylactic co-glycollic acid (PLGA) scaffold implants containing seven parallel-aligned channels, either 450mum (n=19) or 660microm in diameter (n=14). Animals were sacrificed after 1, 2 and 3months. Immunohistochemistry for neurofilament expression was performed. The cross-sectional area of fibrous tissue and regenerative core was calculated. We found that the 450microm scaffolds had significantly greater axon fibers per channel at the 1month (186+/-37) and 3month (78+/-11) endpoints than the 660microm scaffolds (90+/-19 and 40+/-6, respectively) (p=0.0164 and 0.0149, respectively). The difference in the area of fibrous rim between the 450 and 660microm channels was most pronounced at the 1month endpoint, at 28,046+/-6551 and 58,633+/-7063microm(2), respectively (p=0.0105). Our study suggests that fabricating scaffolds with smaller diameter channels promotes greater regeneration over larger diameter channels. Axonal regeneration was reduced in the larger channels due to the generation of a large fibrous rim. Optimization of this scaffold environment establishes a platform for future studies of the effects of cell types, trophic factors or pharmacological agents on the regenerative capacity of the injured spinal cord.