Chronic spinal cord injury (SCI) is a formidable hurdle that prevents a large number of injured axons from crossing the lesion, particularly the corticospinal tract (CST). This study shows that Pten deletion in the adult mouse cortex enhances compensatory sprouting of uninjured CST axons. Furthermore, forced upregulation of mammalian target of rapamycin (mTOR) initiated either 1 month or 1 year after injury promoted regeneration of CST axons.Ourresultsindicatethatbothdevelopmentalandinjury-inducedmTORdownregulationincorticospinalmotorneuronscanbereversedinadults. Modulating neuronal mTOR activity is a potential strategy for axon regeneration after chronic SCI.