Background: Rheumatoid arthritis (RA) is a chronic, relapsing inflammatory and autoimmune multisystem illness that affects the joints. Methotrexate (MTX) is considered by many rheumatologists to be the most important and useful [DMARDs]. Metformin an antidiabetic medication has been reported to exert an anti-inflammatory effect. The rationale of this study is to test the effect of monotherapy with metformin alone or in comparison with methotrexate monotherapy on Adjuvant-induced arthritis (AIA).  Aim of the study: The present study was designed to evaluate the effect of metformin alone and during basal treatment with methotrexate on rheumatoid factor, C-reactive protein, reduced glutathione, tumor necrosis factor- α, arthritis score and histopathological changes. Materials and methods: Rats were classified into: Group I: control normal group. Group II: was not treated (diseased group). Group III was treated with methotrexate (MTX). Group IV:  was treated with metformin. Group V: was treated with combination of MTX with metformin. All treated groups received drugs for 4 weeks. Results: All groups showed significant improvement in all parameters and improvement of the histopathology of the joint. A significant reduction in the score was seen in all treated group at the end of 3rd and 4th weeks. Conclusion: All tested drugs alone or in combination showed improvement of parameters of RA. It is found that all combinations show more efficacy than each drug alone.