Objective : Gyehyuldeung (GHD) has been widely used in oriental medicine for the treatments of cardiovascular and neurological disorders. Thus, its potential facilitatory activity on axonal regeneration was investigated in the rats. Methods: Sprague-Dawley rats were given crush injury at the sciatic nerve and the changes of axon growth after nerve injury on each nerve injury model were investigated with anti-NF-200 antibody, DiI, GAP-43 protein and Cdc2 protein Results : GHD-mediated enhancement of axonal regeneration after crush injury was measured in both qualitative and quantitative ways by immunofluorescence staining with anti-NF-200 antibody and retrograde tracing of fluorescence dye DiI. GAP-43 protein levels were elevated by GHD treatments in the distal injured sciatic nerve and DRG sensory neurons. The neurite outgrowth of DRG sensory neurons was facilitated by GHD treatment when co-cultured with Schwann cells and astrocytes prepared from injured sciatic nerves and injured spinal cord tissues, respectively. It was observed that Cdc2 protein was up-regulated in co-cultured Schwann cells or astrocytes and Cdc2 protein signals were co-localized to a certain extent with those of phospho-vimentin protein. Conclusions : These results suggest that GHD may play a facilitatory role in axonal regeneration by acting on the injured axons and adjacent non-neuronal cells. The current findings may be useful for the development of therapeutic targets through more specific explorations on molecular interactions between herbal components and endogenous factors.