Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a chronic inflammatory process and abnormal wound healing. Tumor Necrosis Factor alpha (TNFα) is considered to play a key role in fibroblast proliferation and increased collagen synthesis. It appears that there is a genetic predisposition to IPF. The genetic associations of TNF-α with IPF have been reported in different cohorts and revealing conflicting results. This study was conducted to evaluate the association of TNF- alpha-308 G/A polymorphism with IPF in Iranian patient by PCR-RFLP method. Materials and Methods: TNFα gene polymorphism at position 308 G/A was examined on DNA extract of 41 cases with IPF defined clinically, radiologically and histologically and compared with 82 unrelated healthy controls who were kidney donors. Results: The understudy population included 20 males and 21 females with the mean age of 50.4 yrs. Data showed that the frequencies of G allele (NO:72) and A allele (NO:10) were 87% and 12% respectively. The frequency of G/G genotype (NO:31) was 76%, followed by G/A (No:10) being 24%.we had no A/A genotype. Conclusion: There was no association between TNF alpha-308 G/A polymorphism and IPF in Iranian patients. (Tanaffos 2006; 5(1): 25-30)