Activation of microglia/macrophages after injury occurs limitedly in the CNS, which finding may explain unsuccessful axonal regeneration. Therefore, the relationship between lipopolysaccharide (LPS)-induced inflammation and recovery of locomotor function of rats after spinal cord injury was examined. High-dose LPS improved locomotor function greater than low-dose LPS, being consistent with the expression of neurotrophic factor (GDNF) in microglia/macrophages. Experiments using GDNF gene mutant mice confirmed that the increase in the GDNF mRNA level, rather than the reduction in the mRNA level of inducible NO synthase, could be correlated with the restoration activity of locomotor function. These results suggest that a higher degree of inflammation leads to a higher degree of repair of CNS injuries through GDNF produced by activated microglia/macrophages.