BackgroundMesalamine is a first-line drug in the treatment of inflammatory bowel diseases, while its intolerance occasionally occurs in clinical practice. Most of adverse reactions are due to the active components, which may lead to step-up treatment, but excipients are sometimes regarded as the chief culprit and can be resolved by transferring to other preparations. Thus, distinguishing different kinds of intolerance is extremely important for clinical decision.Case presentationHere we reported two cases with mesalamine intolerance. One patient with 5-aminosalicylic acid intolerance had similar adverse reactions to the treatment of different preparations, while another patient with excipients intolerance failed to tolerate Salofalk but could take Pentasa with no symptoms. Meanwhile, clinical manifestations were analysed and the previous reports referring to excipients intolerance were summarized. It is interesting to found that the patients with excipients intolerance mainly presented with acute skin symptoms, such as skin rash, urticaria and angioedema. But the adverse effects of 5-ASA in previous reports include fever, headache, rash, nausea, vomiting, dyspepsia, hepatotoxicity, pancreatitis, interstitial nephritis, pneumonitis, pericarditis and so on.Conclusions5-aminosalicylic acid and excipients should be taken into consideration together when mesalamine-related adverse events occur. Of note, a diagnosis of excipient intolerance should be paid more attention in the patients with the presentation of acute skin symptoms.