Objective: Necrotizing enterocolitis has been investigated and debated extensively in recent years; however, there is still no effective treatment. The aim of this study was thus to examine the effects of -estradiol on intestinal injury in rats.Methods: Twenty-four newborn female rat pups were divided into three groups. In group 1 (sham), hypoxia-re-oxygenation was not performed. In group 2 (saline), the rats were injected with saline after hypoxia-re-oxygenation, and the process was repeated for 5d. In group 3 (-estradiol treatment), the rats were subjected to hypoxia-re-oxygenation and then given -estradiol intraperitoneally once a day for 5d. After these procedures, the terminal ileum was removed for analysis.Results: Statistically significant differences in histological grades were found between groups 1 and 2 (p=0.000), groups 1 and 3 (p=0.028), and groups 2 and 3 (p=0.021). There were also differences in TNF- and IL-6 levels between groups 2 and 3 (p=0.000 and p=0.038, respectively) and between groups 1 and 2 (p=0.000 and p=0.000); there was no difference between groups 1 and 3 (p=0.574 and p=0.195, respectively). Electron microscopy examination revealed a decrease in lipid droplets at the apical cytoplasm of the columnar cells in group 2; in group 3, the absorption of the lipids as lipid droplets was similar to that of group 1.Conclusion: In this study, -estradiol was found to decrease the intensity of intestinal injury significantly by inhibiting TNF- and IL-6.