A novel microelectrode modification method is reported for neural electrode engineering with a flake nanostructure (nanoflake). The nanoflake-modified electrodes are fabricated by combining conventional lithography and electrochemical deposition to implement a microelectrode array (MEA) on a glass substrate. The unique geometrical properties of nanoflake sharp tips and valleys are studied by optical, electrochemical and electrical methods in order to verify the advantages of using nanoflakes for neural recording devices. The in vitro recording and stimulation of cultured hippocampal neurons are demonstrated on the nanoflake-modified MEA and the clear action potentials are observed due to the nanoflake impedance reduction effect.