Objective: The purpose of the present study was to investigate the protective effect of aqueous extract of Thamnolia vermicularis Ach (TWA) on acute alcoholic liver injury (AALI) and its mechanism. Methods: The AALI model was induced by gavage of 56% alcohol at a dose of 12 mL/kg of the experiment. Its mechanisms were evaluated by weight loss， liver index， liver function， ability to metabolize alcohol， oxidative stress levels， inflammatory factors， changes in key protein expression and the effects on intestinal flora. Results: TWA significantly reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST)， increased the level of ethanol dehydrogenase (ADH)， improved liver function and accelerated ethanol metabolism in mice. TWA also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in serum and liver， decreased malondialdehyde (MDA) content， and reduced level of oxidative stress in the mouse caused by ethanol. In addition， TWA reduced the inflammatory response of the body by suppressing tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in the liver and serum. TWA enhanced Nrf2 pathway function and inhibited NF-κB pathway activation， thereby inhibiting liver inflammation and improving the antioxidant stress effect in mice with acute alcoholic liver injury. Meanwhile， the expression of CYP2E1， a key protein of alcohol metabolism， was down-regulated to accelerate hepatic alcohol metabolism and reduce hepatic alcohol metabolic injury. TWA promoted the proliferation of Lactobacillus and Bifidobacterium， and reduced the colony numbers of Enterococcus， E. coli and Peptococcus， so improved the intestinal environment. Conclusion: TWA could improve liver function and alcohol metabolism， enhance antioxidant capacity， reduce the level of inflammatory factors， inhibit the expression of key proteins of Nrf2/NF-κB pathway and maintain intestinal homeostasis， so improve AALI in mice.