Aims: To investigate the effects of methylcobalamin (MeCbl) on angiogenesis after peripheral nerve injury.Methods: For in vivo experiments, we used eighteen 6-week-old male Wistar rats. The left sciatic nerve was excised and bridged using the decellularized nerve. Then, rats were randomly divided into MeCbl treated and saline treated groups. At postoperative 7 days, nerves were harvested and evaluated for immunohistochemistry. For in vitro experiments, scratch assay, and tube formation assay were evaluated in the presence or absence of MeCbl using human umbilical vein endothelial cells. Additionally, we performed receptor tyrosine kinase (RTK) assay, RAS protein detective assay and Western blotting to assess intracellular signaling pathways influenced by MeCbl. Statistical analysis was performed using unpaired Student’s t-test or one-way ANOVA with Tukey – Kramer’s multiple comparison test.Results: In the immunohistochemistry for sciatic nerves, the neovascular areas significantly increased in the MeCbl group (p<0.05) compared with the control group. The scratch and the tube formation assay indicated the significant increase for cell migration and angiogenesis in the MeCbl group (p<0.01). In the RTK assay, MeCbl was found to have no effects on the activation of RTKs on the cell membrane surface. However, through the RAS protein assay, it was elucidated that MeCbl activates RAS proteins, downstream of the RTKs. Moreover, Western blotting showed that MeCbl activated the PI3K – AKT – mTOR pathways, which is a downstream signaling cascade of RAS, more than control group.Conclusions: Our study revealed that MeCbl promotes angiogenesis following peripheral nerve injury in a rat model.