〔Abstract〕 To explore the effect of dendrobium officinale polysaccharides (DOP) on necrotizing entero- colitis (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 injec- tion 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 fac- tor-α(TNF-α) , interleukin (IL) -1β, IL-6 and IL-10 were measured by ELISA . The levels of lactate dehydro- genase (LDH) , malondialdehyde (MDA) , superoxide dismutase (SOD) and glutathione (GSH) were detected u- sing commercial kits . The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygen- ase-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 < 0. 01 or P < 0. 001) . The protein expression levels of E-cadherin , Occludin and Claudin-1 were reduced (P < 0. 01 or P < 0. 001) . The concentrations of TNF-α, IL-1βand IL-6 increased , while the concentration of IL-10 decreased (P < 0. 01) . The levels of MDA and LDH increased , while the levels of GSH and SOD decreased (P < 0. 01) . The protein expression levels of Nrf2 and HO-1 increased ( P < 0. 05 or P < 0. 01) . In contrast , DOP intervention groups showed increased body weight and decreased HE scores (P < 0. 05 or P < 0. 01) . The protein expression levels of E-cadherin , Occludin and Claudin-1 increased (P < 0. 05 or P < 0. 01 or P < 0. 01) . The concentrations of TNF-α, IL-1βand IL-6 decreased(P < 0. 05 or P < 0. 01 ) , while the concentration of IL-10 increased ( P < 0. 01) . The levels of MDA and LDH decreased , while the levels of GSH and SOD increased ( P < 0. 05 or P < 0. 01) . The protein expression levels of Nrf2 and HO-1 further increased (P < 0. 05 or P < 0. 01) . Conclusion DOP can ameliorate the pathological damage of necrotizing enterocolitis and enhance the intestinal mucosal barrier function in NEC mice . Additionally , it can also reduce oxidative stress injury and intestinal inflammation in NEC mice . The mechanism may be associated with the activation of the Nrf2/HO-1 pathway by DOP.