The objective of this study is to evaluate the suitability of a mouse middle ear model for testing ossicular replacement materials. Twenty-four BALB/c mice are implanted with the bioglass-ceramic Bioverit II which is coated with a silica-nanostructure or with plain Bioverit II as a control. After 2, 6, and 12 weeks, 4 mice per group are sacrificed and both complete petrous bones are analyzed histologically. All implants revealed in situ an incipient growth of thin connective tissue layers over the surface, followed by a spreading of epithelial cells. The osseogenic response which is increasing with time is more intense in the coated Bioverit II specimens. The absence of inflammatory cells suggests an excellent biocompatibility of the silica nano structure. As the results are comparable to a study with the same materials in rabbits, the mouse model described is highly suitable for evaluation of new ossicular replacement materials. Additionally, by gene expression analysis a more detailed insight into cellular interactions of the middle ear is offered.