Objective: Establish the acute pulpitis model of α7 nAChR gene knockout mice to provide an experimental model for studying the mechanism of α7 nAChR in the course of occurrence and development of pulpitis. Method: Through the open medullary cavity method, a model of pulpits was established on the maxillary first molars of 16 α7 nAChR knockout mice (KO) and 16 wild type (WT) in C57BL / 6 J. Mice were sacrificed, perfused, decalcified and tissues were sectioned at 1, 3 and 7 days after the opening of the established medullary cavity, then observed the pathological condition of pulp tissue by stained with HE and immumohistochemical of NLRP3. Results: The results of HE staining showed obvious vascular congestion and tissue edema in α7 nAChR KO and WT mice near the perforation hole 1 day after the pulp exposure . Inflammatory cells were observed in the pulp cavity, and the inflammatory cells in α7 nAChR KO mice were observed at the bottom of the pulp cavity, while the inflammatory cells in WT mice were mainly observed in the pulp tissue around the pulp hole 3 days after pulp exposure. Inflammatory cells in α7 nAChR KO mice infiltrated into the root pulp, while inflammatory cells in WT mice were mainly concentrated at the bottom of the crown pulp 7 days after pulp exposure. The results of NLRP 3 immunohistochemical staining showed that after detal pulp exposure the α7 nAChR KO mice were significantly severely than WT mice. Conclusion: The pulpitis model of α7 nAChR gene knockout mice was successfully established, and the pulpitis inflammation was deteriorated after α7 nAChR gene knockout in mice compared with WT mice.