Objective: To investigate histopathologically whether grape extract (Vitis Vinifera L), a potent free radical scavenger and can ameliorate the methotrexate -induced intestinal mucositis. Material and Methods: Wistar albino male rats were assigned to 3 groups: Group 1 (n=7) control group: An equal volume of distilled water that used for grape extract was given throughout the 15 days and physiological saline was administered intraperitoneally on the 10th day. Group 2 (n=10) methotrexate group: Rats received an equal volume of distilled water. A single dose of 20 mg/kg methotrexate was given intraperitoneally on the 10th day. Group 3 (n=10) methotrexate-grape extract group: The same dose of methotrexate was applied intraperitoneally on the 10th day. For milliliters grape extract solution was administered for 15 consecutive days. Complete blood counts were analyzed from each rat. Results: The control group showed normal intestinal structure. Group 2 had villus shortening and fusion with variable degrees of epithelial atrophy (p=0.001). The number of crypt cells was decreased and crypt loss was prominent (p=0.007). Inflammatory infiltration and decreased goblet cell number in both villi and crypts were distinctive (p<0.001). Villous and crypt injury, and inflammatory infiltration was less in group 3. In addition, goblet cells were increased. The difference was significant between group 2 and 3 for the jejunum damage (p=0.021). Hemoglobin levels increased in group 3. Conclusion: Present study suggested that grape extract could be useful in the ameliorating intestinal damage caused by methotrexate. Its effect could be attributed to its antioxidant properties. Grape extract may have a clinical application in cancer chemotherapy.