Motor imagery (MI) refers to the mental simulation of an action without overt movement. While numerous transcranial magnetic stimulation (TMS) studies provided evidence for a modulation of corticospinal excitability and intracortical inhibition during MI, the neural signature within the primary motor cortex is not clearly established. In the current study, we used directional TMS to probe the modulation of the excitability of early and late indirect waves (I-waves) generating pathways during MI. Corticospinal responses evoked by TMS with posterior–anterior (PA) and anterior–posterior (AP) current flow within the primary motor cortex evoke preferentially early and late I-waves, respectively. Seventeen participants were instructed to stay at rest or to imagine maximal isometric contractions of the right flexor carpi radialis. We demonstrated that the increase of corticospinal excitability during MI is greater with PA than AP orientation. By using paired-pulse stimulations, we confirmed that short-interval intracortical inhibition (SICI) increased during MI in comparison to rest with PA orientation, whereas we found that it decreased with AP orientation. Overall, these results indicate that the pathways recruited by PA and AP orientations that generate early and late I-waves are differentially modulated by MI.