Background: Tumor necrosis factor -alpha is a proinflammatory cytokine and closely related to hyperandrogenism, anovulation, Insulin resistance and obesity, which are common features in poly cystic ovary Syndrome (PCOS). The association between TNF-alpha and insulin resistance in PCOS patients remains controversial. Aim: To investigate TNF-alpha levels in South Indian women with PCOS and its relation with Insulin resistance. Materials and Method: case-control study 104 women with PCOS and 95 healthy age matched control subjects were recruited for the Study. Standard- physical method and chemiluminescent immuno assay techniques were employed for measurement of anthropometric parameters and plasma sex hormones respectively. Fasting insulin, glucose was measured by standard methods. Serum TNF-a was measured by ELISA and Insulin resistance were measured as HOMA-IR. Result: Our results showed that both serum TNF-alpha (P<0.05) and Insulin resistance (P<0.01) were significantly increased in women with PCOS than control subjects. TNF- alpha was positively correlated with Insulin resistance (Y=0.275; P <0.05) Conclusion: The data obtained from present study showed that TNF-alpha levels in woman with PCOS significantly higher than those in healthy control and contribute to the pathogenesis of insulin resistance and evidence of chronic low-grade inflammation in PCOS patients