Tissue plasminogen activator (tPA) is a protease expressed in CNS by various cells and it is mainly known for its thrombolytic function in the treatment of stroke. While its contribution to myelination within the central nervous system is known, its involvement in peripheral remyelination processes remains to be explored. Indeed, in physiological conditions, Schwann cells, responsible for myelination, express low levels of tPA, however its expression increases following injuries to peripheral nerves. Therefore, our study focused on elucidating involvement of tPA in peripheral nervous system remyelination after a post-sciatic nerve injury. To do so, we realized a sciatic nerve injury in wild-type and tPA-deficient mice. At different time point (from D1 to D14 post-injury), we analyzed phenotypic characterization of Schwann cells by immunochemistry and in situ hybridization. By using electron microscopy, we examined the myelin sheath's ultrastructure and evaluated the characterization of Schwann cells and other cells present during remyelination. Finally, we comprehensively evaluated sensory and motor recovery outcomes post-sciatic nerve injury in both wild-type and tPA-deficient mice. Our preliminary results indicate that wild-type mice reveal earlier remyelination and more pronounced inflammation compared to tPA-deficient mice. Furthermore, we demonstrate that tPA does not impact myelin sheath thickness post-sciatic nerve injury. Finally, regarding functional recovery, we noticed a gait delay in tPA-deficient animals. Deciphering the role of tPA in PNS remyelination offers insights into nerve injury recovery and identifies potential therapy targets for better outcomes in peripheral nerve injury patients.