Objective To compare the therapeutic efficacy of fluid resuscitation with hypertonic or normal saline on the rats suffering explosion injury in closed cabin combined with hemorrhagic shock. Methods One hundred and forty-seven anesthetized male SD rats undergoing explosion injury in a closed cabin where detonator was detonated instantaneously, while they were fixed at the site where the explosive was 11-12cm from the center of thoraco-abdominal junction of the rats. Smog was quickly removed from the cabin. The 10min time point after explosion was set as the zero point to record mean arterial pressure (MAP),and moderate hemorrhagic shock was conducted by uniform femoral exsanguination. One hundred and eight rats were randomly divided into three groups (36 each): control group (no resuscitation), hypertonic saline solution (HSD,75% NaCl/6% Dextran) group (4ml/kg) and normal saline (NS) group (NS:blood loss=3:1). Fluid was given via femoral vein catheter 90min after injury, and the infusion lasted for 5min in HSD group and 30min in NS group. Eight rats were randomly sacrificed in each group at the time points of 150, 210 and 270min to analyze the arterial blood gas and water content in the brain and lung tissues. The other 39 rats were also randomly and equally divided into 3 groups and the treatment was the same as above, but with recording of the MAP and survival rate at the time points of 30, 90, 150, 210 and 270min. Results Six rats died in control group, three died in NS group, and all rats of HSD group survived up to 270min. There were significant differences in survival rate among the 3 groups. The MAP rose obviously in NS and HSD groups at the time point of 150min, while it lowered gradually at 210min and 270min in NS group, but no obvious lowering was found in HSD group, and the difference was significant at 270min among the 3 groups (P<0.05). The water contents in the lung and brain tissues decreased in HSD group but increased in NS group at 150min, 210min and 270min, and the differences were significant among the 3 groups (P<0.05 or P<0.01). Arterial blood gas improvement was detected in both HSD and NS groups. At 210min and 270min, pH and PO2 were higher but lactate level was lower in HSD group than in NS group (P<0.05 or P<0.01). Conclusion HSD could maintain the hemodynamic stability of rats suffering from explosion injury combined with hemorrhagic shock, and its positive effect on arterial blood gas and edema of the lung and brain is superior to normal saline.