Abstract: Objective: To explore the protective effect and mechanism of Aloe bark extract (ABE) on acute alcoholic liver injury. Methods: Firstly, the antioxidant activity of ABE was determined by DPPH, ABTS and hydroxyl radical scavenging tests in vitro. Furthermore, different concentrations (5, 10 μg/mL) of ABE were added to alcohol-induced HepG2 cells for 24 h. The release of cellular aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) production were detected, while the Nrf2, SOD, ADH, IL-6 and IL-1β gene expression were detected by RT-PCR. Male C57BL/6J mice were given 50% ethanol by gavage to cause acute alcoholic liver injury, thus an in vivo animal model were established. Various dose groups (50, 100, 200 mg/kg) were given for three consecutive days, the activity levels of AST and ALT in the serum of the mice in each group were detected, and the content of MDA in the liver was also measured. The pathological changed changes of the liver were observed by H&E staining, and similarly the Nrf2, HO-1, SOD, CAT, ADH and ALDH in liver tissue were measured by RT-PCR. Results: ABE showed significant antioxidant activity in vitro. The IC₅₀ values of DPPH, ABTS and hydroxyl radical scavenging activity of ABE were 2.03, 0.131 and 0.74 mg/mL, respectively. Within the alcohol-induced cell and animal models, ABE could significantly reduce the levels of ALT and AST in cell and mouse serum (P<0.05), reduce MDA in cells and liver tissue (P<0.05). H&E staining showed that ABE could improve hepatic oxidative stress and steatosis induced by alcohol. Molecular mechanism studies had indicated that ABE play a liver-protecting role mainly by directly regulating alcohol metabolism-related enzymes, antioxidant enzymes and inflammatory responses. Conclusion: The ABE can significantly alleviate alcohol-induced liver injury, and may be potential active substance for treatment of the acute alcoholic liver injury.