Previous studies have demonstrated that resuscitation with hypertonic saline and pentoxifylline (HSPTX) attenuates hemorrhagic shock-induced injury when compared with Ringer’s lactate. Liver ischemia/reperfusion (I/R) process can trigger a systemic inflammatory syndrome producing remote organ damage and occurs in major liver resections and transplantation.Aim: To evaluated the effect of the combination of hypertonic saline (7.5%NaCl) and pentoxifylline (PTX) on local and systemic injury during partial liver ischemia/reperfusion.Methods: Wistar male rats underwent partial liver ischemia performed by clamping the pedicle from medium and left anterior lateral segments during an hour under mechanical ventilation. They were divided in to 3 groups: group NS (n=20): rats received 0.9% NaCl (34ml/Kg); group HS (n=20) rats received 7.5% NaCl (0.4ml/Kg); and group HSPTX (n=20): rats received 7.5% NaCl (0.4ml/Kg) + PTX (25mg/Kg). Four and twelve hours after reperfusion blood were collected for determinations of AST, ALT, TNF-α, IL-6, and IL-10. Liver and pulmonary tissues were assembled for liver histology and for liver mitochondrial oxidation and phosphorylation, pulmonary vascular permeability and myeloperoxidade (MPO) analyses.Results: Four hours after reperfusion HS and HSPTX groups presented elevation of AST and ALT serum levels significantly lower than NS group (p<0.05). A significant reduction on mitochondrial dysfunction was observed in HS and HSPTX groups compared with NS group (p<0.05). Elevation in serum TNF- α, IL-6, and IL-10 was similar among three groups (NS, HS, and SHPTX). Pulmonary vascular permeability was significantly lower in groups HS and HSPTX compared with NS group (p<0.05). No differences in pulmonary MPO activity were observed among these three groups. Twelve hours after reperfusion a significant reduction in pulmonary vascular permeability in group HSPTX was observed when compared to groups HS and NS (p<0.05). HS and HSPTX groups showed a reduction in serum IL-6 when compared to NS group (p<0.05). Conclusion: Addition of pentoxifylline to hypertonic saline solution reduces not only the liver damage but also the pulmonary vascular permeability associated to hepatic ischemia reperfusion.