The aim of this study was to assess the efficiency of hyperbaric oxygen alone and in combination with 5-aminosalicylic acid in the acetic acid-induced colitis model, a well-known experimental model of inflammatory bowel disease in rats. Rats were randomly divided into five groups. In the noncolitis control group, rats were given isotonic saline, while in the other groups rats were treated by intracolonic administration of 4% acetic acid. In group 2, the untreated control group, no additional therapy was applied. In groups 3, 4, and 5 hyperbaric oxygen, 5-aminosalicylic acid. and 5-aminosalicylic acid + hyperbaric oxygen therapies were applied, respectively. Administration of acetic acid caused an inflammatory response in all animals. Histopathologic score was significantly higher in group 2 than in any other group. 5-Aminosalicylic acid and hyperbaric oxygen significantly decreased the histopathologic score (P < 0.05). Myeloperoxidase activity was also reduced significantly by 5-aminosalicylic acid (P < 0.05) but not by hyperbaric oxygen. The most prominent ameliorative effect, however, was seen in group 5 and the histopathologic score and myeloperoxidase activity were significantly lower than in groups 3 (P < 0.05) and 4 (P < 0.001). Hydroxyproline level also increased significantly in group 5, but not in groups 3 and 4 (P < 0.001). These findings indicate that hyperbaric oxygen therapy is effective in reducing the extent of colitis induced by acetic acid, although it is not as potent as 5-aminosalicylic acid. The combination of hyperbaric oxygen and 5-aminosalicylic acid, however, led to a much more prominent reduction in the severity of colitis. Hyperbaric oxygen may have a promising place in the treatment of inflammatory bowel disease.