The tubulization repair technique is a useful model for studying peripheral nerve regeneration since it provides quantifiable parameters for assessing the effects of exogenously applied substances on nerve repair. In this study, we observed that the local administration of hyaluronic acid (HA) in a tubular prosthesis at the time of implantation significantly improved the repair process, and that this effect was dependent on the viscosity of the HA preparation. The sciatic nerve of C57BL/6J mice was transected and the proximal and distal nerve stumps were sutured into a polyethylene tube (PT, 0.76 mm i.d.) to bridge a nerve gap of 4 mm. The tubes were implanted either empty, or filled with a low-viscosity (MW = 450 - 1000 kDa) or high-viscosity (MW = 7000 kDa) commercial preparation of HA. After 4 weeks, the PT with the regenerating nerve cables were processed for histological analysis and the total number of myelinated axons was counted using a computer-controlled system. Low-viscosity HA significantly increased peripheral axon regeneration (2191 ± 82 myelinated axons, mean±SEM) compared to the group with empty tube implants (1597 ± 80). This enhanced regeneration was not observed in the group implanted with tubes containing high-viscosity HA (1643 ± 69). The stimulatory effect of exogenous HA on nerve regeneration could be due to its activity on non-neural cell proliferation, migration and differentiation which would lead to faster ingrowth of regenerating axons.