We examined the effect of hypertonic saline resuscitation on histological damage of the liver after hemorrhagic shock and resuscitation in mice. Methods: Male BALB/c mice weighing 24 to 34 g were anesthetized and the left femoral artery was cannulated and blood was withdrawn until a mean arterial pressure of 40 ± 5 mmHg was reached. These levels of hypotension were sustained for 90 min, and resuscitation was made as follows: Sham; animals were anesthetized and catheter was inserted for 90 min, HS+SB; hemorrhage shock for 90 min and resuscitated with hypertonic saline (4 ml/Kg of 7.5% NaCl:HS) and shed blood (SB) at the same time, 2LR+SB; hemorrhage shock for 90 min and resuscitated with lactatedRinger's solution (2 times the volume of the shed blood) and SB.Samples were harvested at 2, 6, 24 and 48 h after hemorrhage and resuscitation. Injury score was defined as the extent of injury of the histological damage of the liver assessed with destroyed hepatocytes group formation, neutrophil infiltration, lipid follicle, vanishing nuclei of the hepatocytes, ballooning of the hepatocytes as follows. 0.5 = minimal injury, 1.0 = mild injury, 2.0 = moderate Injury, 3.0 = severe injury. Results: Histological damage shows the highest score in 2LR+SB group at 2h and HS+SB at 2h group shows significant decrease than 2LR+SB group at 2h (P < 0.01). Conclusion: HS resuscitation reduces the histological damage of the liver at 2h and the small intestine at 6h (published data) after hemorrhagic shock and resuscitation. These findings may have important role in development ofARDS and MOF after hemorrhagic shock and resuscitation.