Some factors include environmental triggers have role in development of intestinal inflammation in inflammatory bowel disease (IBD). A number of patients with IBD, experience improvement in their gastrointestinal symptoms and disease course when avoiding gluten. To highlight this issue we present a 28years old male patient, known case of ulcerative colitis, was admitted to the hospital for a flare-up of his disease. He presented with bloody diarrhea despite the fact that he was on long term variable dose of oral and topical Asacol since 4 years ago and azathioprine 2.5mg/kg/day prescribed for his persistent symptoms since last year. In spite of drug adherence, he experienced 3 flare-ups during past year and refused receiving prednisolone. Colonoscopy demonstrated severe erythema, multiple erosions and friability through the left colon from rectum up to splenic flexure. Histopathological evaluation revealed crypt architecture distortion with moderate increase in lymphoplasmacytic infiltration as well as neutrophilic activity in the form of cryptitis and crypt abscess formation. Upper GI endoscopy followed by duodenal biopsies and serological evaluation were negative for celiac disease. Before considering anti-TNF agents, patient underwent a gluten-free diet (GFD) and with a positive response, it continued for 6 weeks. After 6 weeks GFD his bloody diarrhea was nearly resolved and 12 weeks later most of his symptoms disappeared and entered to the full clinical remission. He stopped the diet and 12 weeks later his symptoms returned and experienced another relapse that again improved on GFD.As an environmental factor, gluten represents a strong antigen that might be implicated in the pathogenesis of at least a number of patients with IBD. Dietary restriction of gluten might be useful in some IBD patients during the exacerbation of their disease.