Objective of the study was to evaluate the efficacy and side effects of methotrexate (MTX) in the treatment of systemic lupus erythematosus (SLE). The results showed that all patients completed 3 months study. MTX patients had significantly improved than the controlled patients: disappearance of skin lesions (76.7 and 35.5 percent) and arthritis (64.3 and 16.7 percent), reduced SLEDAI score (2.27 +/- 1.36 and 4.51 +/- 2.47) and methylprednisolon dose (6.1 +/- 2.0 and 13.16 +/- 7.41 mg/day). The clinical side effects and increased transaminase (GOT and GPT) were significantly higher in the MTX group (30 percent and 9.7 percent, 10 percent and 0.0 percent, 23.3 percent and 0,0 percent) but were mild and transient. In conclusion, MTX conferred a significant advantage in patients with lupus by lowering daily methylprednison dose and decreasing lupus disease activity (specially with dermatitis and arthritis). Simultaneously, it has been well tolerate in lupus patients.