Injuries and diseases that occur in the nervous system are common and have few effective treatments. Previous studies have shown that quercetin has a therapeutic effect on nervous system injuries, but its potential effects on and mechanisms of action related to behavioral recovery and axonal regrowth have not been investigated. Here, we showed that quercetin administration promotes behavioral recovery following sciatic nerve-crush injury in mice. Long-term evaluation showed that mice administered 20 mg·kg-1·day-1 quercetin for 35 days had a greater sensorimotor recovery compared with all other treatment groups. The mechanisms behind these effects were further investigated, and quercetin was found to regulate the expression of genes involved in regeneration and trophic support. Moreover, quercetin increased cyclic adenosine monophosphate expression and downstream pathway activation, which directly leads to neuronal growth activation in peripheral axon regeneration. In addition, quercetin enhanced axon remyelination, motor nerve conduction velocity and plantar muscle function, indicating that the degree of distal portion hypotrophy during the peripheral axon regeneration process was reduced. These results suggest that quercetin accelerates functional recovery by up-regulating neuronal intrinsic growth capacity and postponing distal atrophy. Overall, quercetin triggered multiple effects to promote behavioral recovery following sciatic nerve-crush injury in mice.