Objective After SCI, a series of endogenous processes, including reactive astrogliosis and neuro-inflammatory response, are triggered and resulted in the formation of a degenerative microenvironment in the lesion site.In many studies, this hostile environment, as well as the intrinsic incapacity of the neuron to regenerate, is regarded as an important contributor to the failure of spontaneous anatomical and functional repair of SCI.The present study is to explore the neuroprotective effect of ethyl pyruvate in the damaged spinal cord using a rat model of SCI.Methods Initially, a scratch-wound model was applied to test reactive astrogliosis in vitro.In vivo, astrogliosis, scar formatting and neuroinflammatory response were further assessed with a spinal cord-hemisectined SCI model.In the damaged spinal cord, survival neurons and regenerative axons was identified by TUNEL staining and BDA anterograde tracing, respectively.Finally, functional recovery was valuated by the Basso, Beattie, and Bresnahan open-field scoring, grid-walk test and foot-print analysis.Results In the present study, ethyl pyruvate was found to inhibit reactive astrogliosis in vitro, which was further confirmed in injured spinal cord.In addition, ethyl pyruvate treatment was also shown to attenuate SCI-induced neuroinflammation by decreasing the Iba-1 or CD 11 b-positive inflammatory cells at the lesion site.Importantly, ethyl pyruvate-treated rats showed a significantly greater number of survival neurons and regenerative axons and their behavioral functions were evidently improved.Conclusion Ethyl pyruvate ameliorates the glial microenvironment and promotes spinal cord repair, suggestive of a potent neuroprotective effect against SCI.