Background: Methotrexate (MTx), a cytotoxic drug, causes severe damage of small intestine and alters its oxidative state. Resveratrol (RES) has a powerful anti-oxidant and anti-inflammatory activities. Aim of the study was to assess and compare the effects of different doses of Resveratrol on methotrexate induced jejunal toxicity. Material and methods: Forty Two adult male albino rats were divided into five groups; control group, RES treated group in which rats were subdivided into two subgroups and received low and high doses of resveratrol (RES) orally, MTx group in which rats were given methotrexate orally at a dose of 5 mg/kg daily for thirty days, MTx+ RES L group in which rats received low dose of RES with MTx dose , MTx+ RES H group rats were received RES in high dose combined with MTx dose. After 30 days of treatment, specimens of jejunum were obtained for histopathological, biochemical and immunohistochemical examination. Results: MTx induced epithelial and crypt cellular damage which was corrected by resveratrol and intestine nearly restored its normal structure, better results were gained with the high dose of resveratrol. Also, recovery of histopathological and biochemical findings was gained. Conclusion: this study concluded that Resveratrol could protect jejunum from damaging effect of methotrexate in a dose dependent manner.