Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder and a major cause of disability in adults. Improvements following surgical decompression are limited and patients often remain severely disabled. Post mortem studies indicate that CSM is associated with profound axonal loss. However, our understanding of the pathophysiology of CSM remains limited.To investigate the hypothesis that axonal plasticity plays a role in the recovery following surgical decompression, we adopted a novel preclinical model of mild to moderate CSM. Spinal cord compression resulted in significant locomotor deterioration, increased expression of the axonal injury marker APP, and loss of serotonergic fibres. Surgical decompression partially reversed the deficits and attenuated APP expression. Decompression was also associated with axonal sprouting, reflected in the restoration of serotonergic fibres and an increase of GAP43 expression. The re-expression of synaptophysin indicated the restoration of functional synapses following decompression. Promoting axonal plasticity may therefore be a therapeutic strategy for promoting neurological recovery in CSM.