The present study was undertaken to study the immunotoxic effects of methotrexate (MTX) in male rats. This was done through estimating some interleukines IL-11β, IL-6 and some immunological parameters as SOD, GSH, IgG, IgM, catalase, total Proteins and its fractions, some liver function parameters were also studied including serum AST, ALT, GGT activities and malondialdehyde. In this experimental study, thirty mature male albino rats weighing from 170-180 gm., aging 4-5 months age were used. Animals were classified randomly into 3 parallel groups as following:The1^st group: rats were given distilled water (1 ml) orally daily for 7 weeks and kept as control group, the 2^nd group: rats were given MTX (0.1 mg/100 gm. body weight weekly I.P. for 7 weeks and the 3^rd group: rats were given MTX (0.2 mg/100 gm. body weight weekly I.P. for 7 weeks. At the end of the study, 7 weeks post drug administration, all rats from each group were sacrificed and blood samples were collected into centrifuge tubes for separation of serum for determination of the above mentioned parameters. Methotrexate induced a significant increase in serum activities of AST, ALT, GGT, MDA, IL-6 and IL-1β and a significant decrease in serum activities of SOD, GSH and IgG and IgM as well as serum total protein, albumin and globulins when compared was normal control group. In all studies the effects were dose dependent. Thus patients treated with MTX should be supplemented with antioxidants, hepatoprotectives and immunostimulants to avoid its adverse effects.