Myelin sheath is essential for the rapid propagation of action potentials and proper functions of the nervous system. In the peripheral nervous system, it has been well-known that Schwann cells generate myelin sheath through several stepwise differentiation processes, but the detailed mechanism to regulate Schwann cell differentiation remains unclear. Previously, we demonstrated the involvement of hypoxia inducible factor 1α (HIF1α) in the regulation of peripheral myelination. To further investigate the role of HIF1α in peripheral myelination, we used a conditional knock-out (cKO) mice lacking HIF1α gene in myelinating Schwann cells. An in vitro myelination assay revealed that hypoxic treatment facilitated myelination in wild-type control but not cKO. Unexpectedly, peripheral myelin of cKO mice was formed normally without significant motor deficits. Next, we examined the remyelination in post-injury nerves. In cKO mice, the frequency of uncompacted myelin in regenerating nerve was higher than control mice. cKO mice also exhibited a delayed recovery in a sensory-motor function assessment. The comprehensive analysis of HIF1α regulated gene expression in Schwann cells using a Chromatin integration labeling followed by sequencing technique revealed that HIF1α stabilization by a transient hypoxic treatment increased the expression of several genes associated with Schwann cell differentiation. These findings suggested that HIF1α might be involved in peripheral remyelination after nerve injury through regulation of Schwann cell differentiation.