Background and Objectives: Preterm labor is a serious problem in obstetrics, accounting for 70% of perinatal mortality. High sensitive C - reactive protein (HS-CRP) is a sensitive marker of Inflammation. Our aim in this study was to determine Amniotic fluid hs-CRP concentration and its correlation with pre-Term delivery. Materials and methods: This prospective study was conducted on 90 pregnant women who underwent genetic amniocentesis between the 15th and 20th weeks of gestation. All patients were followed until delivery. Pateints with abnormal karyotype and iatrogenic preterm delivery for fetal and maternal indications were excluded. The samples were carried immediately to the laboratory of Imam Khomaini Hospital Complex, Tehran, Iran for cytogenetic examination and tested for HS-CRP by turbidimetric method. Non parametric tests and receiver-operating characteristics curve analysis were used for statistical purpose. Results: The study showed no correlation between amniotic fluid HS-CRP concentrations with preterm delivery. Maternal serum alpha-fetoprotein (AFP) levels were higher in patients delivered preterm compared with term deliveries (P=0.036). Conclusion: Our results implicated that HS-CRP like other acute phase response markers was not as a possible risk marker of preterm delivery.