Necrotizing enterocolitis (NEC) is a serious condition affecting the neonate that may be responsive to medical management. This study evaluates the efficacy of supplemental oxygen (FiO2 40% and 50%), systemic antibiotics (ampicillin and gentamicin, cephamandole) and oral antibiotics (trimethoprim-sulfamethoxazole, neomycin and gentamicin) in a weanling rat bowel ischemia model induced by a transient (one minute) occlusion of the superior mesenteric artery. Animals were evaluated for overall survival, duration of survival, presence of bowel necrosis or perforation at seven days. Mortality in ischemic controls was 83.8%. This was reduced to 52% by FiO2 of 50%, and 40% with systemic ampicillin and gentamicin (with or without FiO2 50%) (P less than .001). Length of survival was 3.4 days in controls and increased from 5.4 to 5.9 days in rats given FiO2 50% and/or ampicillin and gentamicin (P less than .001). The incidence of bowel necrosis in controls was 60% and was reduced to 25% in rats given systemic ampicillin and gentamicin and 23.3% with 50% FiO2 and the same antibiotics (P less than .001). Systemic cephamandole and oral antibiotics had no beneficial effects.