Diffusion reactions between MgAl2O4 (spinel) single-crystal substrates and epitaxial Al layers were studied by transmission electron microscopy (TEM) imaging and analysis. The specimens were annealed for 10 and 20 h at 893 K in ultra-high vacuum. In addition to plain annealing, we annealed while applying electric fields across the MgAl2O4, either oriented in the direction from the Al to the MgAl2O4 or opposite. TEM revealed that plain annealing enables a diffusion reaction during which the MgAl2O4 region adjacent to the interface becomes depleted of Mg and enriched in Al. An electric field oriented in the direction from Al to MgAl2O4 accelerates the reaction, while a field in the opposite direction retards it. The observations agree with an ion exchange mechanism proposed earlier, implying transport of Mg into the metal. However, Mg transport into the opposite direction also contributes to the reaction. The experimental observations demonstrate that annealing in electric fields can effectively control interface microstructures and properties.