Abstract Background: Necrotizing enterocolitis (NEC) is a severe acute gastrointestinal disease affecting mainly preterm new-borns. The pathophysiology of NEC remains poorly under-stood. Aim of Study: To investigate the diagnostic and prognostic potential of this gut-associated biomarker in the early diag-nostics of NEC, their association with clinically relevant and well-established disease-related parameters, and their capacity to predict the disease course among neonates in neonatal intensive care units in Ain Shams University Pediatrics Hos-pital. Patients and Methods: 23 preterm neonates diagnosed with NEC were recruited randomly and enrolled in this study as the cases group, with corresponding 23 gestational age and birthweight matched preterms with no known intestinal injury or history of abdominal surgery enrolled as controls. All recruited randomly from the neonatal intensive care units of Ain Shams Pediatrics university hospital, during the period from October 2018 till March 2020. Results: The 1st values of IFABP taken at the time of diagnosing NEC showed that mean serum IFABP concentra-tions of the study group were much higher than the control group. In the 2nd values of serum IFABP taken one week after diagnosing NEC showed that the mean serum IFABP concen-trations of the study group became decreased in comparison with IFABP at the time of diagnosis in stages 1 and 2A compared to stages 2B and 3. Conclusion: Serum I-FABP levels are increased in preterm neonates with NEC in comparison to age-matched controls; also serum I-FABP levels are increased according to the severity of NEC. So serial measurements of serum I-FABP levels may be a useful marker for early diagnosis and prediction of disease severity and prognosis in NEC patients.