Objective To investigate the protective effects of Dahuang Mudan against liver injury in rats with acute pancreatitis. Methods Overall, 96 SPF Wistar rats were randomly divided into blank, model, Dahuang Mudan decoction high-, medium-, and low-dose (14, 7, 3. 5 g / (kg·d), respectively), and octreotide (10 μg / ( kg·d)) groups, with 16 animals in each group. The acute pancreatitis model was generated by retrograde injection of 5% sodium taurocholate solution into the pancreaticobiliary duct. before the model and every 12 h after the model. Samples were collected 24 h after the mold. To observe the rats’ general physical signs, serum amylase (AMS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (ChE), and C-reactive protein (CRP) contents were biochemically determined, and hematoxylin and eosin staining used to observe pancreatic and hepatic histopathological changes. ELISA was employed to detect rat liver tissue TNF-α, IL-1β, and IL-6 contents, and western blotting was used to detect the expression of key rat liver PI3K/ Akt pathway proteins. Results (1) Compared with the blank group, the model group rats’ general survival status was relatively poor; their contents of AMS, ALT, AST, and CRP increased and that of ChE decreased. Microscopic analysis of HE staining showed the pancreatic tissue had incomplete structure, and was necrotic and congested with severe inflammatory infiltration; liver cells showed disordered arrangement, and liver tissue showed necrosis, steatosis, and inflammatory infiltration. The TNF-α, IL-1β, and IL-6 contents of the liver tissue homogenate were significantly increased; PI3K, p-Akt, p-NF-κB p65, and Bax protein expression levels decreased and Bcl-2 protein expression increased, especially in the Dahuang Mudan high-dose group, and the difference was statistically significant ( P< 0. 05). ( 2) Compared with the model group, the general condition of the rats in each treatment group improved to varying degrees: the degree of pancreatic tissue edema, congestion, and necrosis visible under the microscope was significantly improved, and liver cell arrangement disorder, necrosis, steatosis, inflammatory infiltration, among others, were alleviated. AMS, ALT, AST, and CRP contents decreased to varying degrees, and the ChE content increased. Liver tissue homogenate TNF-α, IL- 1β, and IL-6 contents decreased; PI3K, p-Akt, p-NF-κB p65, and Bax protein levels decreased; while the levels of Bcl-2 protein increased, especially in the Dahuang Mudan high-dose group, and the differences were statistically significant (P< 0. 05). Conclusions Dahuang Mudan decoction effectively improved the general health, biochemical indicators, and pathological changes to the pancreas and liver of acute pancreatitis model rats. The mechanism of its liver-damage-reducing action may involve regulation of the PI3K/ Akt signaling pathway.