Traditional views consider scar tissue formed in the lesion epicenter after severe spinal cord injury (SCI) as both a physical barrier and chemical impediment for axonal regeneration. Recently, a controversial opinion suggested that astrocyte scar formation aids rather than prevents axonal regeneration in the CNS. Here, following complete transection of the thoracic spinal cord (T8) in rats, we found that scar tissue showed greater growth factor expression at 2weeks than 8weeks post-SCI. Further, tandem mass tag (TMT)-based quantitative proteomic analysis revealed that the components of scar tissue formed in the subacute phase are quite different from that formed in the chronic phase. We also found significantly increased axonal regrowth of sensory axons into the lesion center after chronically formed scar tissue was removed. This indicates that scar tissue formed at the chronic phase actually inhibits axonal regeneration, and that chronic removal of scar tissue may have clinical significance and benefit for SCI repair. Taken together, our study suggests that the features and roles of subacute and chronic scar tissues formed post-SCI is different and scar tissue-targeted strategies for spinal cord regeneration cannot be generalized. Copyright 2018 Elsevier Inc. All rights reserved.