This study aimed to assess of hepatoprotective effect of theabrownin (TB) from Pu-erh tea against lipopolysaccharide (LPS)-induced injury in vivo. A rat model of liver injury was established by injecting LPS (1.5 mg•kg−1) every 3 days. The animals were randomly separated and treated with a placebo, low-dose, medium-dose, or high-dose (0.135, 0.405, and 1.215 g•kg−1, respectively) TB for 21 days. The growth status of the rats was recorded throughout the experiment and at the end of the experiment the liver index was calculated, the enzymatic activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in the liver, and histopathological changes in liver tissues were determined by hematoxylineosin staining. Additionally, serum ALT, AST and alkaline phosphatase activities, and serum total cholesterol, total triglyceride (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol contents were measured. Compared with the control group (healthy animals), LPS-administrated rats exhibited disordered arrangement of hepatocytes, accompanied by extensive inflammatory cells infiltration and focal hepatocyte necrosis, as well as disorganized splenic nodules and indistinct red/white pulp boundaries in the spleen. Furthermore, significant elevations were observed in the spleen index, liver index, serum ALT activity, and serum TG content (P<0.05). High-dose TB significantly reduced the levels of these parameters by 13.69%, 41.10%, 41.34%, and 37.50% (P<0.05), respectively, while also alleviating the LPS-induced histopathological injury in liver and spleen tissues. These results demonstrate that TB exerts some protective effects against LPS-induced liver injury in rats, thus providing a new foundations for the development and therapeutic use of TB.