The aim of this experimental study was to investigate the histopathologic effect of Nigella Sativa oil (NSO) on cisplatin (Cis) induced oral mucositis (OM) in rats. Twenty-four rats were divided into four equal groups. The animals in Group 1 and Group 2 were given 5 mg/kg intraperitoneal (ip) Cis systemically on the 1st, 3rd and 5th days of the study. Additionally, 15 mL NSO were given to the rats in Group 2, with gavage feeding on days 1, 3, 5, 7, and 9. The animals in Group 3 were given per oral 15 ml NSO on days 1, 3, 5, 7 and 9. As the control group, Group 4 received a total of 15 mL 0.9% saline solution divided into 5 doses on days 1, 3, 5, 7 and 9 by oral gavage. On the 14th day, animals were euthanized and buccal mucosa from both sides, including submucosal tissues, were excised and taken to histopathological examination. The mean mucosal thicknesses of the groups were 224.58 μm, 276.1 μm, 323.33 μm, and 331.33 μm, respectively for Groups 1, 2, 3, and 4 (p<0.05). When the degree of mucosal inflammation was examined, the most intense inflammation was detected in Group 1 and the least intense inflammation was in Group 4 (p<0.01). The degree of inflammation in Group 2 and Group 3 were similar to Group 4 (p>0.05). According to the results of this study, NSO, for which anti-inflammatory and antioxidant properties have been shown in previous studies, may also be effective in preventing Cis-induced OM. © Copyright 2020 by Official Journal of the Turkish Society of Otorhinolaryngology and Head and Neck Surgery.