〔Abstract〕 Objective To explore the effect of dendrobium officinale polysaccharides(DOP) on necrotizing enterocolitis(NEC) in neonatal mice and to preliminarily explore the potential molecular mechanisms. Methods Seven-day-old C57BL/6J mice were randomly divided into four groups: control(CTRL) group, necrotizing enterocolitis(NEC) group, low-dose DOP treatment(DOPL+NEC) group and high-dose DOP treatment(DOPH+NEC) group. The NEC model was established by hypoxia, cold stimulation, hypertonic feeding and intraperitoneal injection of lipopolysaccharide(LPS). At the end of the experiment, the small intestine tissues were collected. The general condition of the mice was observed, and body weight was recorded. Hematoxylin-eosin(HE) staining was used to observe pathological changes in the small intestine tissues. The expression levels of E-cadherin, Occludin and Claudin-1 were detected by immunohistochemistry and Western blot. The concentrations of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, IL-6 and IL-10 were measured by ELISA. The levels of lactate dehydrogenase(LDH), malondialdehyde(MDA), superoxide dismutase(SOD) and glutathione(GSH) were detected using commercial kits. The expression levels of nuclear factor erythroid 2-related factor 2(Nrf2) and heme oxygenase-1(HO-1) proteins were detected by immunohistochemistry and Western blot. Results Compared with the CTRL group, the NEC group exhibited decreased body weight and increased HE pathological scores(P