The role of cytokines and growth factors in the pathophysiology of neonatal necrotizing enterocolitis (NEC) is not defined clearly yet. The aim of this study was to determine the effects of recombinant human granulocyte colony stimulating factor (G-CSF) on intestinal cells in hypoxia-induced experimental NEC in rats. The study was experimented on Sprague Dawley rat pups. Group 1 (untreated, n = 7) rats were subjected to hypoxia-reoxygenation (H/O) and then were returned to standard conditions. Group 2 (G-CSF treated, n = 7) rats were subjected to H/O, and then were treated with G-CSF (100 microg/kg enterally) for 5 days. Group 3 was served as nonhypoxic controls. All animals were killed on day five, and histological examination was performed on intestinal samples. There were no histopathological changes in the control group. The histological findings in untreated rats were similar to those seen in neonatal NEC, with destruction of villi and crypts with extension to the muscularis layer. Intestinal damage was mild in group 2 and these histological changes were better than group 1, and worse than group 3. The mean of histologic grade of group 1 was 2.4 (range 2-3), and in the group 2, it was 1.2 (range 0-2). A difference was found when two groups were compared with each other (P < 0.05). In an experimental model of NEC, G-CSF could have a protective effect on intestinal damage.