Objective: To explore the effects of hypertonic sodium saline (HSS) resuscitation on the liver damage of rats at early stage of severe scald. Methods: Fifty-six SD rats were divided into sham injury group (SI, n=8), lactated Ringer's solution group (LRS, n=24), and group HSS (n=24) according to the random number table. Rats in group SI were sham injured without resuscitation, while rats in the other two groups were reproduced deep partial-thickness to full-thickness scald model with 30% total body surface area on the back. Rats in group LRS were resuscitated with LRS, while rats in group HSS were resuscitated with 300 mmol/L sodium ion solution according to the Parkland formula. Blood of abdominal aorta and liver of 8 rats in group SI immediately post injury and in the other two groups at post injury hour (PIH) 2, 8, and 24 respectively were collected. Then liver water content was determined by dry-wet weight method. Serum content of alanine aminotransferase (ALT) and aspartate transaminase (AST) was detected by automatic biochemical analyzer. Serum content of tumor necrosis factor α (TNF-α), interleukin-1 (IL-1), and high mobility group box 1 (HMGB1) was determined by enzyme-linked immunosorbent assay. Liver content of malondialdehyde (MDA) and superoxide dismutase (SOD) was detected by ultraviolet spectrophotometer. Pathologic changes of liver were observed by HE staining. Data were processed with one-way analysis of variance and SNK test. Results: (1) At PIH 2, 8, and 24, liver water content of rats in group LRS was higher than that in group SI and group HSS (P<0.05 or P<0.01). (2) At PIH 2, serum ALT content of rats in the three groups was similar (with P values above 0.05). At PIH 8 and 24, serum ALT content of rats in group HSS and group LRS was higher than that in group SI (P<0.05 or P<0.01), and serum ALT content of rats in group HSS was lower than that in group LRS (with P values below 0.01). At PIH 2, 8, and 24, serum AST content of rats in group HSS and group LRS was higher than that in group SI (with P values below 0.01). At PIH 2 and 8, serum AST content of rats in group HSS was lower than that in group LRS (P<0.05 or P<0.01). (3) At PIH 2 and 8, serum TNF-α content of rats in group LRS was (123±39) and (153±38) pg/mL respectively, higher than that in group SI [(60±18) pg/mL] and group HSS [(85±10) and (94±16) pg/mL respectively, with P values below 0.01]. At PIH 8, serum TNF-α content of rats in group HSS was higher than that in group SI (P<0.05). At PIH 24, serum TNF-α content of rats in the three groups was similar (with P values above 0.05). At PIH 2, 8, and 24, serum IL-1 content of rats in group LRS was (122±35), (141±30), and (122±31) pg/mL respectively, and that in group HSS was (80±12), (93±15), and (80±11) pg/mL respectively, all higher than that in group SI [(40±17) pg/mL, with P values below 0.01]; serum IL-1 content of rats in group HSS was lower than that in group LRS (with P values below 0.01). At PIH 2, serum HMGB1 content of rats in the three groups was similar (with P values above 0.05). At PIH 8 and 24, serum HMGB1 content of rats in group LRS was (0.386±0.146) and (0.590±0.188) ng/mL respectively, higher than that in group SI [(0.050±0.027) ng/mL] and group HSS [(0.143±0.038) and (0.309±0.095) ng/mL respectively, with P values below 0.01]. At PIH 24, serum HMGB1 content of rats in group HSS was higher than that in group SI (P<0.01). (4) At PIH 2, 8, and 24, liver MDA content of rats in group HSS and group LRS was higher than that in group SI and their liver SOD content was lower than that in group SI (with P values below 0.01); liver MDA content of rats in group HSS was lower than that in group LRS and their liver SOD content was higher than that in group LRS (with P values below 0.01). (5) Compared with those of rats in group SI, liver cells of rats in group LRS showed massive steatosis at each time point, and liver cell-edema appeared at PIH 8 and 24; while liver cells of rats in group HSS showed little steatosis only at PIH 8 and 24, and the liver cell-edema never appeared. Conclusions: Compared with LRS, HSS resuscitation can alleviate liver injury of rats at the early stage of severe scald through relieving inflammatory mediators and reducing degree of oxidative stress, etc.