Objective To induce an NLRP3P>- / -P> mouse model of ulcerative colitis ( UC ) using different concentrations of dextran sulfate sodium ( DSS) and different administration times, and to analyze and evaluate the advantages and disadvantages of the preparations to provide a more suitable animal model for the study of UC pathogenesis in humans and the development of therapeutic drugs. Methods Forty-eight male NLRP3P>- / -P>specific-pathogen-free mice were divided randomly into blank, 2. 5% 7 d, 3% 7 d, and 3% 5 d groups (n = 12 mice per group). UC mouse models were induced using combinations of different concentrations and administration times of DSS. Body weight, DAI( disease activity index)score, hematoxylin and eosin (HE) staining, colon length, and related indicators (interleukin IL-6, tumor necrosis factor (TNF)-α, and tight junction protein (ZO-1)) were observed and evaluated. Results (1)UC membrane type was induced in each group with different concentrations and administration times. (2)Mouse body weight decreased, the fecal occult blood became more positive, the DAI score increased, and more mice died with increasing DSS concentration and administration time. (3)Longer administration time and higher concentration of DSS were also associated with more severe damage to the intestinal mucosa, as shown by HE staining. (4) Immunohistochemistry showed that the inflammatory factors TNF-α and IL-6 were increased in the model group compared with the blank control group, while expression of ZO-1 was decreased compared with the blank group. Conclusions (1)Administration of 2. 5% or 3% DSS for 7 days or 3% DSS for 5 days can induce UC in NLRP3P>- / -P> mice. (2)The combination of DAI score, HE staining, the detection of related indicators, and mouse survival rate indicated that NLRP3P>- / -P> mice treated with 3% DSS for 5 days produced the most suitable UC model to study the clinical manifestations and drug treatment of UC.