Case summaryThis report describes a 4-year-old cat with chronic intermittent haematochezia and faecal incontinence of 7 months’ duration. Investigation revealed severe colonic multifocal mucosal ulcerations and infiltration of the mucosal lamina propria by large numbers of periodic acid–Schiff-positive macrophages. Fluorescence in situ hybridisation analysis of colonic biopsies revealed multifocal clusters of intracellular Escherichia coli. Treatment with fluoroquinolones for 6 weeks led to a complete resolution of clinical signs.Relevance and novel informationThe findings reveal that mucosally invasive E coli can also be associated with granulomatous colitis in cats and indicate the need for diagnostic testing of mucosal samples for E coli and other infectious agents.