Abstract: Peripheral nerve injuries are rather common but efficacy of its treatments are often suboptimal. Schwann cells, the principal glial cells in the peripheral nervous system, play a critical role in axon regeneration following peripheral nerve injury． Their specific role and underlying mechanisms remain inadequately understood． The influence of Rheb, a significant energy regulator in Schwann cells, on axonal regeneration following peripheral nerve injury is investigated in this work, to analyze the potential mechanisms involved． Immunostaining of SCG10 was employed to assess the regeneration length in Schwann cell-specific Rheb knockout mice (Rheb cKO) after sciatic nerve crush injury． Regeneration length of neurites was compared among groups after administration of lactic acid, glucose, lactate transporter inhibitors to cultured dorsal root ganglion (DRG) neurons． Western blot analysis was conducted to measure levels of phosphorylated AKT (p-AKT) in Rheb cKO mice and cultured DRG neurons. Axonal regeneration was found to enhance in Rheb cKO mice． Content and release of lactate were significantly elevated in Rheb knockout Schwann cells． Treatment with lactate promoted longer neurite regeneration in cultured DRG neurons． Expressions of p-AKT in Rheb cKO mice and lactate-treated DRG neurons increased． Ablation of Rheb in Schwann cells leads to increased lactate production． It is concluded that lactate from Schwann cells participates in axonal regeneration by modulation of the PI3K-AKT signaling pathway．