Occlusal disharmony is induced by various conditions such as the loss of teeth and inappropriate vertical dimension of crowns, bridges, or dentures. Occlusal disharmony sometimes causes indefinite complaint syndromes, which may be associated with astrocytic hypertrophy and the reduction of numbers of neuronal somata and their dendritic spines in the hippocampus. Microglia monitors the condition of neurons and responds to their degeneration accompanying with astrocytes. However, the effect of occlusal disharmony on the microglia has not yet been investigated. We artificially increased the occlusal vertical dimension by placing dental resin on the upper molars in mice and immunohistochemically investigated the effects of the increase in the vertical dimension on microglia of the hippocampal formation using an antibody against ionized calcium-binding adaptor molecule 1 (Iba-1), a marker protein for microglia. We measured the area occupied by Iba-1-immunoreactive microglia in the hippocampal CA1 region and dentate gyrus 1, 3, and 5 days after increasing the vertical dimension, and compared it with that of control mice. The hippocampal CA1 region contains vulnerable neurons and the dentate gyrus durable neurons. We found that the areas occupied by microglia in the hippocampal CA1 region increased, with the peak on the third day after increasing the vertical dimension, and it gradually declined by the fifth post-operative day. However, such an increase of the area occupied by microglia was not seen in the dentate gyrus. In conclusion, abnormal mastication may activate microglia in the area harboring vulnerable neurons, but not in the area harboring durable neurons.