The proliferation and migration of Schwann cells (SCs) are essential in the process of peripheral nerve repair. A large amount of studies focused on the promotion of the growth of SCs for cell based therapy. Gastrodin (GAS), the main constituent of a Chinese traditional herbal medicine named Gastrodia elata Blume, has been reported to be associated with neuroprotective properties. Besides, GAS activated MAPK and PI3K signaling pathways which are often involved in growth of nerve cells were also reported. Based on the hypothesis that GAS may have an effect on SCs growth, we studied the effect of GAS on rat RSC96 Schwann cells (SCs) and further explored the underlying mechanism. Various concentration of GAS (0μM, 50μM, 100μM, and 200μM) was used for treatment of RSC96 SCs, with the cell proliferation and gene expression of several neurotrophic factors to be detected. Regulation of MAPK and PI3K signaling pathways were assayed by detecting phosphorylation of ERK1/2 and Akt. The results showed that GAS could effectively promote proliferation of RSC96 SCs in a dose- and time-dependent manner. The best performance was obtained at the concentration of 200μM. Exploration of the underlying mechanism showed that GAS probably affects SCs metabolism through inhibiting ERK1/2 phosphorylation and activating Akt phosphorylation in RSC96 SCs. This study may provide reference for its application in treatment of peripheral nerve injuries.