The diagnosis of ulcerative colitis is suggested by the symptoms of abdominal pain, rectal bleeding, and diarrhea. As there is no gold standard for diagnosis, the ultimate diagnosis relies on a combination of history, endoscopic finding, histologic features, and negative stool studies for infectious agents.

• Stool specimens are collected for analysis to exclude infection and parasites, since these conditions can cause colitis that mimics ulcerative colitis.
• Blood tests may show anemia and an elevated white blood cell count or sedimentation rate (commonly referred to as sed rate). An elevated white blood cell count and sed rate both reflect ongoing inflammation in the colon.
• Other blood tests may also be checked including monitoring the kidney function, liver function tests, iron studies, and C-reactive protein (another sign of inflammation).
• There is some evidence that a stool test for a protein called calprotectin could be useful in identifying patients who would benefit from colonoscopy. Calprotectin seems to be a sensitive marker of intestinal inflammation, so elevated levels suggest inflammatory bowel disease in the right setting. This test alone, however, cannot distinguish between different diseases causing the inflammation so should be used with caution.
• Confirmation of ulcerative colitis requires a test to visualize the large intestine. Flexible tubes inserted through the rectum (sigmoidoscopes and colonoscopes) permit direct visualization of the inside of the colon to establish the diagnosis and to measure the extent of the colitis. Small tissue samples (biopsies) can be obtained during the procedure to determine the severity of the colitis.
• A barium enema X-ray may also indicate the diagnosis of ulcerative colitis. During a barium enema, a chalky substance is administered into the rectum and injected into the colon. Barium is radiopaque and can outline the colon on x-ray pictures. A barium enema is less accurate and useful than direct visualization techniques in the diagnosis of ulcerative colitis.

Knowledge of the extent and severity of the colitis is important in choosing among treatment options.

Some newer diagnostic modalities include video capsule endoscopy and CT/MRI enterography. Video capsule endoscopy (VCE) might be useful for detection of small bowel disease in patients with a diagnosis of UC with atypical features and who might be suspected of actually having Crohn's disease. In a study in 2007, VCE confirmed the presence of small bowel disease in about 15% of patients with ulcerative colitis with atypical features or unclassified inflammatory bowel disease. This might be useful diagnostic modality in this specific patient population.

CT and MRI enterography are imaging techniques which use oral contrast agents consisting of PEG solutions or low concentration barium to provide more adequate luminal distension. These have been reported to be superior to standard imaging techniques in the evaluation of small bowel pathology in patients with Crohn's disease. They have also been shown to provide adequate estimations of disease severity in ulcerative colitis (with some under- and overestimations).

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