Methotrexate (MTX) is a chemotherepeutic agent and immune system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy. Silkworm (Bombyx mori) larvae can be used as a bioreactor for the production of low-cost vaccines against different infectious diseases due to their huge value as a health food, especially for cardiac and diabetic patients.In the present study, about 200 fetuses from female rats were examined. We divide pregnant female rats into five groups; group 1 used as negative control received distilled water, group 2 used as positive control and received buffer of Bombyx mori larvae extract, group 3 was treated with MTX at the 12 th day of gestation (at organogenesis phase), group 4 was treated with Bombyx mori larvae extract at 7 th , 9 th , 11 th ,13 th and 15 th days of gestation (during the organogenesis period), & group 5 was injected by MTX the 12 th day of gestation as well as bombyx mori larvae extract at 7 th ,9 th ,11 th ,13 th and 15 th days of gestation. Animals of all groups will be sacrificed on the 20 th day of gestation periods. Then all fetus rats were removed for examination. Livers of all fetus rats were removed for histological and biochemical examination. The morphological examination of the fetuses showed that MTX causes growth retardation represented by a decrease in fetal body weight, body length and tail length. In addition, MTX induced an elevation in the examined liver oxidative stress biomarkers plus myeloperoxidase activity and a decrease in reduced glutathione content and catalase activity. Histopathological studies of fetal liver tissues showed congestion of central vein in MTX group and ballooning degeneration of hepatocytes, perivascular inflammatory cells infiltration and strong deposition of collagen fibers. Noteworthy, Bombyx mori larvae induced marked improvement in injuries associated with MTX administration.