Objectives: Although pentoxifylline produces various beneficial effects following adverse circulatory conditions, it is not known whether this agent has any effects on gut lipid metabolism after trauma-hemorrhage and resuscitation. The aim of this study, therefore, was to determine whether or not administration of pentoxifylline after trauma-hemorrhagic shock has any salutary effects on gut ketogenesis. Design:. A prospective, controlled animal study. Setting: A university research laboratory. Subjects: Fifty-six male Sprague-Dawley rats. Interventions: Rats underwent a midline laparotomy (i.e., trauma-induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the shed blood volume was returned in the form of lactated Ringer's solution. The animals were then resuscitated with four times the volume of maximal bleedout with lactated Ringer's solution over 60 mins. Pentoxifylline (50 mg/kg body weight) or an equivalent volume of normal saline was infused intravenously over 100 mins during and after resuscitation. For in vivo lipid loading, one milliliter of olive oil was given intraduodenally on the completion of resuscitation. Blood samples from portal vein and carotid artery, as well as enterocytes from proximal small intestine, were obtained at 1.5 hrs after fat feeding. Measurements and Main Results: Mitochondrial fatty acid β-oxidation enzyme (i.e., palmitoyl- coenzyme A dehydrogenase) activity, as well as portal and arterial plasma β- hydroxybutyrate values, were determined. Palmitoyl-coenzyme A dehydrogenase activity in villus tip cells and plasma β-hydroxybutyrate values in portal vein and carotid artery were significantly reduced after trauma-hemorrhage and resuscitation. Pentoxifylline administration, however, significantly increased mitochondrial fatty acid β-oxidation enzyme activity and portal plasma β-hydroxybutyrate concentration without significantly affecting arterial concentrations under such conditions. Conclusion: Pentoxifylline promotes gut ketogenesis following trauma-hemorrhage and resuscitation.