Objectives: This study aims to determine whether promoter -238 G/A polymorphism in tumor necrosis factor-alpha (TNF-α) gene is associated with susceptibility to rheumatoid arthritis (RA) in Iranian population and serum level of TNF-a. Patients and methods:This case-controlled study was performed on two groups including 90 RA patients (20 males, 70 females; mean age 50.3 years; range 26 to 65 years) and 90 healthy controls (21 males, 69 females; mean age 48.6 years; range 27 to 63 years). We determined the frequency of -238 G/A TNF-a gene polymorphism by polymerase chain reaction restriction fragment length polymorphism. We measured the serum level of TNF-a using enzyme-linked immunosorbent assay method. Also, we determined the association of serum TNF-a level with the polymorphism in RA patients.