The milling of powder is a common practice for the production of many ceramic components. Nevertheless, the milling of ceramic powder involves many mechanical-chemical interactions. In the present study, the interactions during the milling of a Ba5Nb4O15 powder are investigated. Though the particle size of the powder is reduced after milling, more barium ions are released into the slurry with increasing milling time. The release of Ba2+ during milling modifies the resulting microstructure and crystalline structure of sintered specimen. The microstructure is refined; the periodicity of cations within the layered perovskite structure is decreased with the increase of milling time. As a consequence, the permittivity and quality factor of Ba5Nb4O15 microwave ceramic are decreased.