Abstract: Background and Objective: Cisplatin is an antineoplastic, platinum derivative used in the treatment of various cancers. Mucositis is a notable side effect of cisplatin treatment. Rutin (vitamin P1) is a drug with antioxidant, anticancer, antidiabetic and antimicrobial properties. The aim of this study was to biochemically, histopathologically and immunohistochemically investigate the effect of rutin on cisplatin-induced mucositis of the small intestine (jejunum) in rats. Materials and Methods: Twenty four rats were divided into four groups with six animals in each group: healthy group (HG), cisplatin-only group (CCG), 50 mg kg–1 of rutin plus cisplatin group (RG-50) and 100 mg kg–1 of rutin plus cisplatin group (RG-100). Rutin or distilled water were administered via an oral gavage. One hour after the administration of rutin or distilled water, the CCG, RG-50 and RG-100 were intraperitoneally injected with 5 mg kg–1 of cisplatin once every 2 for 8 days. At the end of this period, all the animals were sacrificed using a high-dose anesthetic and their small intestines (jejunum) were removed for biochemical and histopathological procedures. Differences between the groups were analyzed using a one-way analysis of variance, followed by Dunnett’s multiple comparisons test. Results: The levels of oxidants increased in all the cisplatin-treated groups, whereas those of antioxidants decreased. Rutin administered at a dose of 100 but not 50 mg kg–1 reduced oxidant levels and increased antioxidant levels to those of healthy tissues. Histopathologically, tissue damage was observed in jejunal tissue of the rats administered only cisplatin, whereas treatment with 100 mg kg–1 of rutin prevented cisplatin-induced histopathological damage. In the group administered 50 mg kg–1 of rutin, jejunal tissue showed a near-normal appearance, except for mildly dilated congested blood vessels. As shown immunohistochemically, rutin prevented cisplatin-induced jejunal damage more effectively when administered at a dose of 100 mg kg–1 than 50 mg kg–1. Conclusion: Rutin may be useful in the prevention of cisplatin-induced jejunal mucositis.