Environmental pollution with microplastics (MPs) can have a negative impact on human health. Certain findings point to the relationship between MP and the development of inflammatory bowel diseases (IBD). We investigated the effect of MP consumption on the severity of chronic colitis in male C57BL/6 mice. The MP effect was modeled by drinking water consumption with a suspension of 5 μm PS particles at a concentration of 10 mg/L replacement for 12 weeks. Chronic colitis was induced by three seven-day cycles of 1% DSS consumption (starting from the 8th, 29th and 50th days of the experiment). We investigated inflammatory infiltration, the goblet cell volume fraction and the highly sulfated and neutral mucins content in them, the endocrine cell number, the ulcerative-inflammatory process prevalence, changes in the gene's expression encoding tight junction proteins, glycocalyx components proapoptotic factor Bax and proliferation marker Mki67 in the colon, and TNFα, IL-1β, IL-6 and IL-10 cytokines content in the serum. In healthy mice, MP did not cause pathological changes in the colon; however, indirect data indicate an increase in colon permeability. In chronic colitis, MP leads to higher prevalence of all pathological changes in general, and ulcers in particular, in a greater number of crypt abscesses and enteroendocrine cells. MP consumption leads to a more severe chronic colitis course.