Electroporation of cells in target tissues is performed using microneedles having integral electrode structures. In a first embodiment, a pair of electrode structures are disposed on opposite sides of a substance delivery opening on a needle or other tissue-penetrating shaft. In a second embodiment, a first electrode structure is disposed on the needle and a second electrode structure is disposed on an attached base. The electrode structures are spaced closely together and relatively low voltages are applied to achieve electroporation-enhanced substance delivery.