Aim: Ischemia/reperfusion (I/R) injury is one of the major problems in intestinal transplantation (ITx). Polimorphnuclear neutrophils (PMNs) mediate lung injury as a consequence of the systemic inflammatory response induced after IRI of the small bowel graft. The aim of the present study was to evaluate the effects of different TNF-α inhibition concepts on PMN infiltration of recipient lung and expression level of graft cytoprotective markers as well. Methods: Orthotopic small bowel transplantation was performed in an isogenic model in male Lewis (LEW) rats. Grafts were flushed with UW solution and stored for 6hrs at 4°C before implantation. The TNF-α inhibitor groups received either infliximab (I) (8 mg/kg b.w. i.v. immediately after reperfusion), etanercept (E) (1 mg/kg b.w. s.c.; pre reperfusion, PODs 1,3,5,7) or pentoxifylline (P) (50 mg/kg b.w. i.p pre reperfusion; 25 mg/kg b.w. i.p PODs 1-5). Controls (C) received no further treatment. Tissue samples of proximal and distal graft were taken 20 min, 12h, 7d and 6 mths after reperfusion (each n=6 per time point and group) for immunohistology (HSP70). Lung sections (12h, 7d and 6 mths after reperfusion) were stained for Myeloperoxidase (MPO, specific staining of neutrophil granulocytes). Significant differences were evaluated by multifactorial analysis using two-way ANOVA and Bonferroni post test. Results: Seven day survival was significantly improved following TNF-α inhibition with infliximab (I 100% vs. C 60%: p< 0.05). Beyond POD 7 survival was 100% in all groups. TNF-α inhibition with infliximab correlated with significantly enhanced accumulation of cytoprotective markers (HSP-70) in small bowel grafts. Moreover, MPO stain revealed a significant reduction of neutrophil infiltration of the lung following TNF-α inhibition with all three treatment modalities. Discussion: PMN infiltration of recipient lung was significantly reduced after short-term TNF-α inhibition. Single shot treatment with infliximab correlated with a significant increase in HSP-70 expression in intestinal grafts. These findings may help to: 1. improve injury of distant organs after ITx and 2. ameliorate initial graft injury after I/R, which is believed to exert long-term effects on graft outcome by activating innate immunity, thus contributing to chronic allograft enteropathy.