PURPOSE: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of premature infants. Daikenchuto, a Japanese herbal drug, has several effects on the digestive system, so we investigated its preventive effects in a rat model of NEC. METHODS: NEC was induced in newborn rats via asphyxia (100% N2 for 90 s; every 4 h) + LPS (4 mg/kg/day [administered orally on days 0 and 1]). The effects of Daikenchuto were evaluated in four groups (control: 0 g/kg/day, I: 0.3 g/kg/day, II: 0.6 g/kg/day, and III: 1.0 g/kg/day). Daikenchuto was administered into the stomach through a microcatheter. The incidence and severity of NEC were pathologically assessed using the NEC grade in accordance with Dovorak's previous report. Cell positivity for inflammatory cytokine (IL-6) was also evaluated. RESULTS: Daikenchuto reduced the incidence of NEC in control, Groups I, II, and III to 68.7, 30.0, 30.7, and 13.3%, respectively. High-dose Daikenchuto significantly improved the incidence of NEC, and the rate of IL-6 positive cells in group III was significantly lower than in the control group (p = 0.04). CONCLUSION: We evaluated the effect of Daikenchuto against NEC and found that it reduced the incidence rate of NEC due to a decrease in the IL-6 production.