Necrotizing enterocolitis (NEC) remains a lethal condition for many premature infants. Peroxisome proliferator-activated receptor-gamma (PPAR-y), a member of the nuclear hormone receptor family, has been shown to play a protective role in cellular inflammatory responses; however, its role in NEC is not clearly defined. We Sought to examine the expression of PPAR-gamma in the intestine using an ischemia-reperfusion (I/R) model of NEC, and to assess whether PPAR-gamma igonist treatment would ameliorate I/R-induced gut injury. Swiss-Webster mice were randomized to receive sham (control) or I/R injury to the gut induced by transient Occlusion Of Superior mesenteric artery for 45 min with variable periods of reperfusion. I/R injury resulted in early induction of PPAR-gamma expression and activation of NF-kappa B in small intestine. Pretreatment with PPAR-y agonist, 15d-PGJ(2) attenuated intestinal NF-kappa B response and I/R-induced gut injury. Activation of PPAR-gamma demonstrated a protective effect on small bowel during I/R-induced gut injury. (c) 2008 Elsevier Inc. All rights reserved.