Background and aim: Animal studies have shown that Nigella Sativa oil can accelerate the wound healing process. The aim of this study was to evaluate the preventive effect of Nigella Sativa oil on the connective tissue inflammation in rats undergoing chemotherapy. Materials and methods: In this animal-experimental model, 32 rats were divided into the control and the treatment groups. The treatment group was pretreated by 400 micro l/kg NS oil once a day for 15 days then both groups received chemotherapy. The injections of the treatment group were continued throughout twelve days. All rats were euthanized 12 days later then their buccal mucosa was assessed histopathologically. Results: Our results showed that the connective tissue inflammation score in the treatment group was significantly lower than the control group. Conclusion: According to our finding, pretreatment with Nigella sativa has some therapeutic effect on stomatitis due to chemotherapy in rats.