BackgroundPeripheral nerve injury (PNI) causes motor and sensory defects, has strong impact on life quality and still has no effective therapy. Glycyrrhizic acid (GA) is one of the most widely used in traditional Chinese prescriptions and as a flavoring additive in the food industry; the aims of the study were to investigate the effects of GA during sciatic nerve regeneration in a mouse model of sciatic nerve crush injury. MethodsWe established peripheral nerve crush model and investigated the effects of GA. We further studied the potential mechanism of action of GA by Western blotting, fluorescence immunohistochemistry, and PCR analysis. ResultsGA improves the sensory and motor functions of crushed nerve by preventing Schwann cell loss, axonal loss and promoting remyelination of sciatic nerve. Affected by GA, the inflammatory response in the distal part of the sciatic nerve was reduced. Finally, the neuroprotective properties of GA may be regulated by the nuclear factor (NF)‐κB pathway. ConclusionsOur data suggest that GA can effectively alleviate PNI, and the mechanism involves mediating inflammatory response by suppressing NF-κB pathway activation. Thus, GA may represent a potential therapeutic intervention for nerve crush injury.