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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. For controlling the disease activity, various therapeutic modalities are used. Each of them have advantages and limitations. This study analyzes effectiveness and toxicity of methotrexate (MTX) on liver and lipid functions in selected RA patients and controls.This study included samples of patients with RA who were on MTX therapy and had long-term follow-up. The control and patient samples were used for analysis of lipid parameters, inflammatory markers as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), essential mineral accumulation, and liver and kidney function test.Hemoglobin was reduced in RA patients; however, ESR, CRP and pain on the visual analog scale were significantly higher as compared to controls. Their alanine aminotransferase, aspartate aminotransferase and uric acid were within normal ranges. Serum magnesium was significantly reduced in RA patients. They showed higher values for zinc, phosphorous, and copper. They had borderline dyslipidemia.MTX was found to be safe and effective for treatment of RA. The liver function test of RA patients was normal. They had disturbances in mineral accumulation, suggesting the requirement of mineral evaluation and supplementation especially of magnesium in RA patients. The treatment was beneficial in reducing inflammation and reducing the activity of the disease. The treatment was also beneficial for lipid parameters reducing the risk of cardiovascular disease. The study supports MTX as the good choice for treatment of RA.