To explore the effect of mirror box therapy based on the mirror neuron (MN) system of the primary motor cortex (M1), we examined if direct (without a mirror) and indirect (with a mirror) observation of self-movement in healthy subjects induced changes in motor evoked potential (MEP) evoked by transcranial magnetic stimulation (TMS). MEPs were elicited from the first dorsal interosseous (FDI) and the flexor carpi radialis (FCR) muscles. Somatosensory evoked potentials (SEPs) during self-movement observation were also recorded. Both observations of self-movement with and without a mirror increased MEP amplitude. In addition, increase in MEP amplitude was specific to the prime mover muscle involved in the observed movement. The SEPs increased similar to the MEPs during both observations of self-movement with and without a mirror. We conclude that although the MN system can be activated by observing self-movement in a manner similar to that achieved by observing movement of another person, there were no detectable effect on corticospinal excitability that were specific to movements observed with a mirror.