During liver ischemia, the drop in mitochondrial energy causes cellular damage, which is aggravated after reperfusion. This injury can trigger a systemic inflammation, also producing remote organ damage. Several substances have been employed to reduce this inflammatory response during liver transplantation, liver resections and hypovolemic shock.Aim: To evaluate the effects of hypertonic saline solution and the best timing of administration to prevent organ injury during experimental liver ischemia/reperfusion.Methods: Animals underwent one hour of warm liver ischemia followed by reperfusion. One hundred-twenty rats were allocated into six groups (n=20). S: sham; C: control animals submitted to parcial liver ischemia; ISSpi: rats received NaCl 0.9% 3.4mL/kg, 15 min before ischemia; HTSpi: rats received NaCl 7.5% 0.4mL/kg, before ischemia; ISSpr: rats received NaCl 0.9% 15 min before reperfusion; HTSpr: rats received NaCl 7.5% before reperfusion. Four hours after reperfusion blood was collected for AST, ALT, IL-6 and IL-10 analyses. Evans blue dye was intravenously administrated to eight animals from each group. Rats were killed for liver histology, phosphorylation of liver mitochondria, edema of liver tissue and pulmonary vascular permeability analyzes.Results: HTSpr group presented elevation of AST (1984±207 UI/L) and ALT (1539±208 UI/L) significantly lower than C (AST 3141±303 UI/L, ALT 2903±347 UI/L) and ISSpr (AST 3169±218, ALT 2791±245 UI/L) groups. The comparisons of HTSpi group to ISSpi or to C groups were not statistically significant. Additionally HTSpr group showed AST and ALT levels significantly lower than HTSpi group (AST 2691±257 UI/mL, ALT 2484±328 UI/mL). No significant differences in IL-6 and IL-10 levels were observed. A significant reduction on mitochondrial dysfunction was observed in HTSpr group compared to ISSpr and C groups (p<0.05). Also ADP/O ratio was significantly reduced in HTSpi group (1.63±0.032) compared to HTSpr (1.83±0.039). Liver tissue edema was significantly lower in HTSpr group (69.8±0.4%) compared to ISSpr (72±1,1%) and C (73±1,4%) groups. Pulmonary vascular permeability was significantly lower in HTSpr group (148±17 mg EBD/g tissue) compared to ISSpr (282±35 mg EBD/g tissue) and C (280±52 mg EBD/g tissue) groups. No significant differences in myeloperoxidase activity were observed. The liver injury histological score was significantly lower in HTSpr group (8.1±1.32) compared to HTSpi group (11.4±0.93).Conclusions: HTS ameliorated liver and lung injuries in experimental liver ischemia/reperfusion. Infusion of HTS in pre-reperfusion period is crucial to accomplish the best results.FAPESP 05/042267