Cigarette smoking is a major risk factor for gastrointestinal disorders, such as peptic ulcer, 
Crohn’s disease (CD), and several cancers. The mechanisms proposed to explain the role of smoking in 
these disorders include mucosal damage, changes in gut irrigation, and impaired mucosal immune 
response. Paradoxically, cigarette smoking is a protective factor for the development and 
progression of ulcerative colitis (UC). UC and CD represent the two most important conditions of 
inflammatory bowel diseases, and share several clinical features. The opposite effects of smoking on 
these two conditions have been a topic of great interest in the last 30 years, and has not yet been 
clarified. In this review, we summarize the most important and well-understood effects of smoking in 
the gastrointestinal tract; and particularly, in intestinal inflammation, discussing available 
studies that have addressed the causes that would explain the opposite effects of smoking in CD and 
UC.