Methotrxate (MTX) has become the standard of care and first-line therapy for patients who have RA and consider as a gold standard of treatment for RA. The role of MTX in the treatment of RA has now been well established. The use of MTX treatment of RA inhibits proliferation of the lymphocytes, reduces signs and symptoms this disease, reduces progression damage of the joints and improves quality of life outcome. Progranulin (PGRN) acts a role in autoimmune inflammatory, has important function in several processes including immune response. Present study has conducted to find the effect of MTX drugs as a therapeutic target for RA patients because of its ability to bind with tumor necrosis factor receptor (TNFR), with progranulin, obestatin and with other kidney parameter. A serum of 65 Iraqi males patients suffering from RA was newly diagnosis without taking (MTX) drugs (G1), and the same patients in G1 after 2 months treatment with MTX drugs in Low-dose (G2), and (35) meals healthy control groups (G3). Results showed significant increased levels in progranulin, obestatin and uric acid in newly diagnosis of RA and there was significant positive (+ve) and negative (-ve) correlation between progranulin and (creatinine, uric acid) respectively in G1 and there was a high significant positive (+ve) and negative (-ve) correlation between progranulin and (uric acid, creatinine) respectively. © Advanced Scientific Research. All rights reserved