Background: The severity of acute pancreatitis results from the transmigration and activation of leukocytes within the pancreas and release of proinflammatory mediators that transform a local injury into a systemic inflammatory response like lung injury. Adhesion molecules play an important role in this transmigration process. Expression of PCAM-1 (CD 31), VCAM-1 (CD 106), P and E-SELECTIN on vascular endothelial is essential for regulating leucocyte trafficking from blood vessels into tissue during inflammatory deseases. The aim of this study was to evaluate the therapeutic approach of volume therapy with HBOC-301 with and without isovolemic hemodilution (IHD) with regard to the survival rate and expression of adhesion molecules in pancreatic tissue in pigs suffering from acute necrotizing pancreatitis. Methods: After approval of the local ethics committee 39 pigs were anesthetized, endotracheally intubated and normoventilated. After laparotomy the pancreatic duct was canulated. After 30 min. equilibration (M0) AP was induced by a combination of intravenous cerulein and intraductal glycodeoxycholic acid. Fifteen min. and 75 min. after induction of AP animals were randomized to isovolemic (PAOP-constant) hemodilution with 10% HES 200,000/0.5 plus HBOC-301 (+ 0.6 g dl-1 plasmatic Hb; Oxyglobin®, Biopure, USA) (IHD+HBOC) or to HBOC-301 (+ 0.6 g dl-1 plasmatic Hb) (HBOC), or to hemodilution with Ringer`s solution (IHD RINGER) to a hematocrit (Hct) of 15%. After six hours abdomen was closed and animals were extubated. After six days (144 hours) surviving animals were sacrified. For immunostaining of vascular adhesion molecules on lung vessels, slides were stained with monoclonal pig antibodies (Ab) against PECAM-1, VCAM-1 E- and P- SELECTIN. Fluorescein isothiocyanate (FITC) -conjugated anti-pig IgG was used as a secondary Ab. Evaluation of expression FITC-stained adhesion molecules was based on the method described by Tang and Hendricks for detection of PECAM. Statistical analyses were performed using the Kruskal-Wallis and Hohns test (significance p<0.05). Results: The survival rate at the end of the observation period was higher in the IHD+HBOC group (10/13) (p<0.001) and in the HBOC-group (9/13) (p<0.001) compared to the Ringer group (2/13) (p=0,001 Kruskal-Wallis Test). The expression of adhesion molecules did not differ among the groups. Conclusion: The therapeutic application of HBOC-301 was able to improve survival after induction of severe AP. The endothelial cell surface expression of PCAM-1, VCAM-1, P and E-SELECTIN in the lung tissue is detectable but did not show significant differences in this model.