Background: Progranulin (PGRN) has significant functions in several processes, including immune response and the development of cancer. This study aims to research the relationship between the ratio of serum progranulin/tumor necrosis factor (TNF) alpha and the rheumatoid arthritis (RA) activity. Methods: This study included 35 patients with rheumatoid arthritis whom we collected their complete history with personal and family history included in addition to 30 seemingly healthy individuals as a normal control group. In addition to clinical examinations, laboratory tests, and serum progranulin level and TNF-alpha by the Enzyme-linked Immunosorbent Assay (ELISA). Results: There were significant increases in Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), Rheumatoid Factor (RF), PGRN and TNF alpha in the diseased group compared to the control group. The serum levels of PGRN and TNF alpha in the rheumatoid arthritis community were significantly higher than in the control group. In the RA community, there was a positive association between the PGRN/TNF alpha ratio and Disease Activity Score in 28 joints (DAS28) score and RF. The relationship between PGRN and the severity ratio was significant. The relationship between TNF alpha and the severity ratio of the disease were highly significant. Also, a significant relationship between the PGRN/TNF alpha ratio and DAS28 score was significant. Conclusion: An important correlation between circulating levels of PGRN and TNF-alpha, and activity of the disease was in RA patients.