Although the role of many small proteoglycans in regeneration of the nervous system has been established, little is known about the involvement of large proteoglycans. In this study, we evaluated the effects of aggrecan, a high molecular mass proteoglycan, on Schwann cells in vitro and investigated its effects on axonal regeneration after sciatic nerve tubulization. The number of regenerated axons and their morphometrical parameters were determined in vivo. Aggrecan increased the number and viability of Schwann cells in vitro. Similarly, the number of regenerated fibers increased significantly when aggrecan was applied in vivo, but there were no alterations in the morphometrical parameters. These results indicate that aggrecan contributes to the regeneration of peripheral axons and has a positive effect on the Schwann cells.