Background and aim of the work: Ulcerative colitis (UC) is a chronic gastrointestinal health problem that can be mistaken for many other infective and non-infective chronic diarrheal diseases. Its relation to chronic intestinal amoebiasis needs to be investigated especially if the cases are out of control. This work aims at evaluating the relation between intestinal amoebiasis and UC. Patient and methods: A group of twenty five patients diagnosed as uncontrolled UC and another group of twenty- five patients with controlled UC were included in this cross sectional analytic study. Both groups were subjected to detailed history taking, clinical examination, routine laboratory investigations, abdominal ultrasonography and colonoscopy with biopsy taking and histopathological examination. Fresh stool samples were collected for measurement of calprotectin by enzyme linked immunosorbent assay (ELISA) and detection of Entamoeba histolytica (E. histolytica) by microscopy and antigen detection. Data were collected, analyzed and compared between both groups. Results: Most of UC signs and symptoms were more presented among the uncontrolled than the controlled group of patients. E. histolytica infection was found to be more prevalent among the uncontrolled (52%) than the controlled (8%) UC patients (P 0.002). Conclusion: Intestinal amoebiasis is more prevalent among uncontrolled cases of UC than the controlled cases and could play an important role in failure of treatment.