Abstract: Background and Objective: Rheumatoid arthritis is a chronic inflammatory disease with relatively high prevalence and if uncontrolled can lead to high morbidity. Biological agents especially, anti-tumor necrosis factors have an important role in controlling disease activity in rheumatoid arthritis today, but in practice, high price makes many patients not able to use them. Usually, effective alternative drugs could be valuable. Pentoxifylline shows anti-tumor necrosis factors-alpha effects in vitro and in vivo and it could be a good candidate. This study evaluates the effect of adding pentoxifylline to the treatment of rheumatoid arthritis with synthetic disease modified anti-rheumatic drugs as an adjuvant therapy. Methodology: Pentoxifylline was added to the treatment regimen of 16 patients with rheumatoid arthritis who had active disease despite receiving synthetic disease modified anti-rheumatic drugs. Disease activity was compared before and few weeks after of pentoxifylline usage. Results: The patient and physician global assessment of disease activity and the number of tender joints were significantly improved after receiving pentoxifylline (p-value = 0.012, 0.03 and 0.02). Also, measures of disease activity score in 28 joints, simple disease activity index and clinical disease activity index were significantly improved (p-value = 0.03, 0.012 and 0.011). Changes in swollen joints counts, erythrocyte sedimentation rate, C-reactive protein, hemoglobin and platelet count were not significant. Conclusion: Pentoxifylline may play a role in the control of disease activity in rheumatoid arthritis.