Peripheral nerve long gap defects are a clinical challenge in the regeneration field. Despite the wide variety of surgical techniques and therapies, autografting is the "gold standard" for peripheral nerve gap reconstruction. The pathological process of Wallerian degeneration from the time of acute injury to efficient regeneration requires several weeks. Regeneration time is critical for nerve reconstruction. Immunological demyelination induced by anti-galactocerebroside antibodies plus guinea pig complement was used to shorten the treatment time. Based on an antigen-antibody complex reaction, the demyelinating agent induced an acute and severe demyelination, leading to the pathological process of Wallerian degeneration during the demyelinating period. This method was used to treat a 12 mm-long sciatic nerve defect in rats. The control groups were injected with one of the demyelinating agent components. The results indicated that anti-galactocerebroside antibodies plus guinea pig complement can significantly shorten treatment time and promote nerve regeneration and functional recovery. In addition, the demyelinating agent can increase the mRNA levels of nerve growth factors and can regulate inflammation. In conclusion, treatment with anti-galactocerebroside antibodies plus guinea pig complement can promote axonal regeneration. This therapy provides a novel method to improve functional recovery in the treatment of long nerve defects.