Methotrexate (MTX) is a chemotherapeutic drug that is widely used in the treatment of malignant tumors and rheumatic disorders. This work aims to study the protective effect of folic acid on the ovary affected by methotrexate. Materials and Methods: Sixty healthy, adult female albino rats were classified into six groups (10 animals each). Group I: Served as control group. Group II: The rats received folic acid in a daily oral dose of (250ug/kg b.w) for four weeks. Group III: Included rats which received an I.P injection of MTX (1mg/kg b.w) once weekly for four weeks. Group IV: The animals were concomitantly treated with MTX and FA as the same previous doses, period and routes of administration. Group V: The animals were concomitantly treated with MTX and FA as the same previous doses, routes of administration for eight weeks. Group VI: Included rats which received an I.P injection of MTX (1mg/kg b.w) once weekly for four weeks then left without treatment for another successive four weeks. Results: The following results from our study were decreased number of ovarian follicles, multiple degenerated and atretic follicles with vacuolation of the oocyte cytoplasm, disturbed oocyte in some follicles with marked apoptotic bodies inside the oocyte and granulosa cells. On the other hand, rats received folic acid (FA) following treatment with MTX revealed more or less apparent normal architecture. Conclusion: FA proved to have remarkable protective effect against toxicity of MTX by minimizing the previous degenerative changes.