OBJECTIVE: To investigate oral microbiota dysbiosis and cytopathological changes in oral mucosa of murine chronic colitis model and the correlation between them. METHODS: Dextran sodium sulfate (DSS) induced chronic colitis was established in SPF C57BL/6 male mice, oral microbiome characterization was performed using 16S rRNA gene sequencing, and cytopathological and immunohistochemistry assessment was performed in oral mucosa. RESULTS: When chronic colitis was induced, the overall microbial composition of the oral microbiome was altered with increased abundance in phylum Proteobacteria (82.2%), Actinobacteria (2.6%) and decreased abundance in Firmicutes (12.7%), Bacteroidetes (1.1%). Among the top 10 most abundance genera, Streptococcus was the only genera significantly decreased in colitis mice oral cavity. Meanwhile, oral epithelial hyperplasia was identified in the murine chronic colitis model, and the ki67 expression was significantly upregulated in oral epithelium (p < 0.05). The chronic course of colitis did not lead to obvious inflammatory infiltration in the oral mucosa. Spearman analysis indicated a strong inverse correlation (r = -0.52, p = 0.03) between oral Streptococcus and epithelium thickness. CONCLUSIONS: The chronic colitis mice displayed epithelial hyperplasia in the oral mucosa without obvious inflammatory infiltration, which might be associated with oral dysbiosis, especially a decreased abundance of Streptococcus.