Sepsis often results in severe pulmonary dysfunction. Via the thoracic duct, the lung is the first organ exposed to gut derived mediators released into the mesenteric lymph. It has been shown that an acute insult to the gastrointestinal (GI) tract, results in inflammatory mediator release into mesenteric lymph inducing pulmonary dysfunction (Deitch EA, Shock 2004). Aim: To investigate whether enteral immunonutrition during sepsis results in a reduced inflammatory response of the GI tract and therefore improving pulmonary function. Methods: Mesenteric lymph was obtained from lymph fistula donor rats. Saline or LPS (5mg/kg, sepsis model) were injected ip, thereafter control lymph (CL) or sepsis lymph (SL) were collected. Additionally SL was collected during enteral immunonutrition with long chain fatty acids (SL-OO, olive oil, or SL-SFO, soybean/fish oil). CL, SL, SL-OO, or SL-SFO were reinfused into the jugular vein of separate recipient rats for 2 h (3ml/h). Thereafter the lung tissue was harvested, stained with hematoxylin-eosin and analyzed for 1. perpendicular parenchyma thickness of the alveolar wall (oxygen diffusion), 2. myelo-peroxidase (MPO) positive cells (inflammatory response) 3. TUNEL positive cells (apoptosis, n=6 rats per group, n=30 optical sections per rat). Results: Sepsis increased TNFα release into mesenteric lymph about 99 fold within the first two hours (TNFα pg/ml, CL vs SL, 0-2h: 120±21 vs 11877±1130*, 2-4h: 158±36 vs 3501±2089*, 4-6h: 172±66 vs 132±27, *p<0.005). Enteral immunonutrition during sepsis reduced the TNFα output into the mesenteric lymph significantly (TNFα pg/ml, 0-2h: SL 11877±1130, SL-OO 2330±1279*, SL-SFO 2605±1802*; 2-4h: SL: 3501±2089, SL-OO 896±661*, SL-SFO 981±412*, *p<0.05 vs SL). SL infusion induced a significant increase in alveolar wall thickness, whereas infusion of SL-SFO had on effect ([µm] NaCl 9±0.2, SL 15±0.4*, SL-SFO 9±0.3; *p<0.001 vs NaCl or SL-SFO). The number of MPO or TUNEL positive cells were significantly increased after infusion of SL and markedly reduced after infusion of SL-SFO (cells/optical section MPO: NaCl 6±1; SL 53±2*, SL-SFO 19±1; TUNEL: NaCl 4±1; SL 13±2*; SL-SFO 1±0.05; *p<0.01 vs NaCl or SL-SFO). Conclusions: Mediators in sepsis lymph induce pulmonary dysfunction, such as an increased distance for oxygen transport, inflammatory reaction and apoptosis. The lung may be protected by an enteral immunonutrition containing long chain fatty acids. Products of chylomicron formation like apolipoprotein (apo) A-IV might be involved, since it was shown that apo A-IV potently reduces acute inflammation (Vowinkel, J Clin Invest 2004). Supported by DFG GL 311, 3/1.