Introduction: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal (GI) tract and involved 10 -20 percent of general population and result in decreased quality of affected individuals. Because multiple suspected etiologies in IBS pathogenesis, various drugs and methods have been offered for its management. Regarding mucosal inflammation in the pathogenesis of IBS, anti- inflammatory drugs, such as mesalasine, reported that is effective in IBS treatment. However, previous documents have different results and we assessed the clinical efficacy of mesalasine in some patients with IBS.Methods: In this double blined randomized clinical trial, 44 individuals with documented IBS, based on Rome III criteria that reffered to gastroenterology clinics of the Zahedan University of Medical Sciences in Zahedan, southest of Iran, were enrolled.All of patient allocated to rececive either mesalasine 500 mg (group A) or identical placebo (group B) three times per day for six weeks. We assessed and analysed IBS symptoms and global IBS symptoms at 0, 4 and 8 weeks.Results: The mean age who received the mesalazine were 40.9-8.8 and 37.6-13.4 years in the case and control group, respectively (P=0.399). The condition of the initial disease severity of the patients whichwas recorded based on the IBS protocol (symptom severity scale (IBS-SSS) did not have any statistically meaningful difference. Significantly more patients in the mesalasine group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks and 8 weeks after initiation of treatment (86% compared with 54%, p=0.021).Conclusion: Mesalasine is an effective drug for mangment of irritable bowel syndrome and it is better to evaluate at larger study for its efficacy.