Methotrexate (MX) is a drug with multiple physiological effects on the body. The objective of this search is to evaluate the enhancing action of folic acid on the blood profile of MX-treated rabbits. 30 female rabbits were divided into 3 groups and each group consisted of 10 animals. CON group, which included healthy rabbits, did not receive any treatment, while the MX group included animals which were injected intraperitoneally with methotrexate once a week. Finally, FO-MX rabbits received a combined dose of oral folic acid with methotrexate. The duration of the experiment lasted 4 weeks and after completion the animals were slaughtered and the marrow was collected. The results demonstrated that MX caused megaloblastic anemia which was characterized by erythroid hyperplasia, megaloblastoid polychromatophilic rubricytes, macromyelocytes and meta-myelocytes. While the FO-MX group showed a good prognosis and improved health. We concluded that co-administration of FO with MX ameliorated the adverse changes of MX, so we recommend that further studies be conducted to evaluate and understand the mechanism of effects of these drugs against the toxicity of the MX.