Unilateral damage to the forelimb region of the sensorimotor cortex (FLsmc) results in time-dependent changes in neuronal activity, structure and connectivity in the contralateral motor cortex of adult rats. These changes have been linked to facilitation of motor skill learning in the less-affected/ipsilesional forelimb, which is likely to promote its use in the development of behavioral compensation. The goal of this study was to determine whether an early post-lesion-sensitive time period exists for this enhanced learning and whether it is linked to synaptogenesis in the contralesional motor cortex. Rats were trained for 21 days on a skilled reaching task with the ipsilesional forelimb beginning 4 or 25 days after unilateral ischemic (endothelin-1-induced) FLsmc lesions or sham operations. As found previously, reaching performance was significantly enhanced in rats trained early post-lesion compared with sham-operates. In rats trained later post-lesion, performance was neither significantly different from time-matched sham-operates nor strikingly different from animals trained earlier post-lesion. In layer V of the contralesional motor cortex, stereological methods for light and electron microscopy revealed significantly more total, multisynaptic bouton and perforated synapses per neuron compared with sham-operates, but there were no significant differences between early- and late-trained lesion groups. Thus, there appears to be a sensitive time window for the maximal expression of the enhanced learning capacity of the less-affected forelimb but this window is broadly, rather than sharply, defined. These results indicate that relatively long-lasting lesion-induced neuronal changes are likely to underlie the facilitation of learning with the less-affected forelimb.