BACKGROUND: Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder, affecting 5-10% of women of reproductive age. Major complications of PCOS include infertility, obesity, endometrial hyperplasia, endometrial cancer, insulin resistance, hyperandrogenism, and cardiovascular issues. This study aims to investigate the polymorphism of the Insulin Resistin (RETN) gene at positions - 420 C\G and + 299 A\G in relation to the susceptibility to PCOS. METHODS: This case-control study included 198 participants (100 diagnosed with PCOS and 98 normal controls). Two single nucleotide polymorphisms of the RETN gene - 420(C/G) (rs1862513) and + 299(G/A) (rs3745367), were analyzed using the PCR-RFLP method. Genomic DNA was extracted from blood samples using a DNA extraction kit. The PCR product was digested with restriction enzymes BbsI and AluI, and the results were analyzed by electrophoresis on an agarose gel. Statistical analysis determined the association of the genotypic and allelic variations with PCOS. RESULTS: The findings indicate no significant association between the RETN gene polymorphism and PCOS. DISCUSSION: Our study found that RETN gene polymorphisms do not appear to play a significant role in PCOS susceptibility in the Iranian population. These results suggest that other genetic or environmental factors may contribute more significantly to the development of PCOS. Further research with larger sample sizes and additional genetic markers is necessary to understand the genetic basis of PCOS fully.