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To examine whether glyburide inhibits bone destruction caused by traumatic occlusion in a rat occlusal trauma model., Excessive mechanical stress, such as traumatic occlusion, induces expression of IL-1β and may be involved in bone resorption. NLRP3 inflammasomes have been linked to IL-1β expression, but it is currently unclear whether glyburide, the inhibiter of NLRP3 inflammasome, suppresses occlusal trauma in rats., Male SD rats aged 7weeks were used. In the trauma group, the occlusal surface of the maxillary first right molar was raised by attaching a metal wire to apply occlusal trauma to the mandibular first right molar. In the trauma+glyburide group, the NLRP3 inhibitor glyburide was administered orally every 24hours from 1day before induction of occlusal trauma. Rats were euthanized after 5 or 10days, and the maxillary first molars were harvested with the adjacent tissues for histopathological investigation. Immunohistochemical expression of IL-1β, NLRP3, and RANKL was also assessed., On day 5, bone resorption was significantly greater in the trauma group compared with the control group or the trauma+glyburide group, and there were significantly higher numbers of osteoclasts and cells positive for IL-1β, NLRP3, and RANKL in the trauma group., In this study, glyburide inhibits bone resorption by traumatic occlusion in rats. It suggests that the NLRP3/IL-1β pathway might be associated with bone resorption induced by traumatic occlusion.