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Ochratoxin A (OTA) is a mycotoxin often found in cereals and agricultural products. There is unequivocal evidence of renal carcinogenicity of OTA in male rats, although the mechanism of action is unknown. Several reports suggest that exposure to OTA resulted in oxidative stress, genotoxicity and DNA damage. Therefore, the aim of the current study was to evaluate the protective effects of aqueous extract of Inula crithmoides growing in Egypt against OTA-induced mutagenicity and oxidative stress. Forty male Sprague-Dawley rats were divided into four groups and treated for 15 days as follows: control group and the groups treated with OTA (3 mg/kg b.w), I. crithmoides extract alone (370 mg/kg b.w) and OTA+I. crithmoides extract. Blood and tissue samples were collected for different biochemical analyses. Bone marrow micronucleus test and blood for random amplified polymorphism DNA-PCR (RAPD-PCR) method were performed to assess the antigenotoxic effect of the extract. The results indicated that OTA induced toxicological effects typical to those reported in the literature and increased the frequencies of MnPCEs in bone marrow. The RAPD-PCR analysis revealed the appearance of new bands in DNA resulting from genetic alteration. The extract alone was safe and succeeded in counteracting the oxidative stress and protect against the cytotoxicity resulting from OTA.