In peripheral nerve transection injury, continuity of axons as well as that of the basal lamina is disconnected. In such case, migrating Schwann cells (SCs) would be the only axonal guidance at an early stage of regeneration. However, it takes a few days for the dedifferentiated SCs to start migration, while axonal growth begins a few hours after injury. Consequently, the axons without guidance extensively branch out and wander off at the lesion, resulting in aberrant reinnervation. Therefore, enhancing SCs migration could be an attractive therapeutic strategy. In this study, we investigated the effects of the in vivo nerve predegeneration on SC migration and the time course of these changes. In our analysis, we established a novel animal model by nerve transplantation from S100-GFP mice (in which SCs constitutively express green fluorescent protein driven by the S100B promoter), by which SC migration could be exclusively visualized. Our results showed that SCs acquire the maximal migration ability with 14-day predegeneration, but subsequently it gradually decreased. There was a correlation between the time course of the changes in SC migration and the number of activated macrophages. These findings suggest that using predegenerated nerve grafts in repairing the transected nerves could facilitate SC migration into the recipient nerve stump. This technique could be beneficial for early establishment of axonal guidance and possible functional improvement after transection injury. (C) 2009 Elsevier Ireland Ltd. All rights reserved.