Background: Preterm infants are born with limitations in their digestive ability due to anatomical and functional limits. Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in the preterm infant. Calprotectin is a 36 kDa protein present in the cytoplasm of the neutrophil has antimicrobial and apoptosis inducing activities. Fecal calprotectin is resistant to degradation and has been proposed as a useful marker of gastrointestinal inflammation. Aim of the work: To explore role of fecal calprotectin as a noninvasive marker of gastrointestinal injury in preterm infants in order to detect its usefulness in diagnosis of necrotizing enterocolitis. Furthermore, to evaluate usefulness of fecal calprotectin to predict necrotizing enterocolitis severity . Patients and methods: this study included preterm infants ≤ 34 weeks gestational age, they divided into two groups. Group Ι: cases group with manifestations of feeding intolerance. Group ΙΙ: preterms achieved full gavage feeding without manifestations of feeding intolerance. All neonates were subjected to history taking, clinical examination, laboratory investigations (complete blood count, C-reactive protein, arterial blood gases and electrolytes) and serial determination of stool calprotectin. Results: There was a highly significant increase in fecal calprotectin in patients with NEC than controls and there was a highly significant increase in its fecal level in died patients than living one. Also, significant increase in fecal calprotectin level with increasing severity of NEC. Conclusion: Fecal calprotectin could be a noninvasive diagnostic and prognostic biomarker for necrotizing enterocolitis