Abstract: Objective To explore whether neurotrophin receptor-interacting MAGE homolog (NRAGE) is involved in the intestinal ischemia-reperfusion (I/R) and its effect on the apoptosis of intestinal epithelial cells and the expression of occludin protein. Methods The level of NRAGE protein after the rat small intestine I/R was detected by immunohistochemical (IHC) In vivo. The level of NRAGE protein and mRNA in IEC-6 cells after hypoxia and reoxygenation were tested by Western blot and RT-PCR respectively in vitro. The IEC-6 cells were divided into four groups, including NRAGE overexpression by lentivirus infection (Lv-NRAGE group), interference (sh-NRAGE group), lentivirus control (Lv-control group), and normal control group without lentivirus infection (NC group). The apoptosis of IEC-6 cells after infection was analyzed by flow cytometry. The level of the tight junction protein occludin was detected by Western blot. Results The expression of NRAGE were highly increased in intestinal mucosa epithelial cells after I/R (P<0.01). The proteins and mRNA levels of NRAGE were increased after 6 h of hypoxia in IEC-6 cellsin vitro. Compared with the Lv-control group, the early apoptosis rate was raised (P<0.01) and the level of occludin was reduced (P<0.01) in Lv-NRAGE group; while the early apoptosis rate was reduced (P<0.01) and the level of occludin was raised in sh-NRAGE group(P<0.001). Conclusion NRAGE may be involved in intestinal I/R and promote the apoptosis and decrease occludin expression of intestinal epithelial cells.