Objective Based on the TLR4 / MYD88 signaling pathway to study the protective effect of Dahuang Mudan Decoction on the rat model of acute pancreatitis ( AP ) made by retrograde pancreaticobiliary duct injection. Methods 96 Wistar rats (SPF grade) were divided into: sham operation group, AP model observation group, octreotide positive control group, Dahuang Mudan Decoction high, medium and low dose groups according to the random number table method . Except for the sham operation group, which was injected by retrograde with normal saline through the pancreaticobiliary duct, the other groups were modeled by retrograde injection of 5% sodium taurocholate solution through the pancreaticobiliary duct, followed by drug intervention for 6 days. To observe the general living conditions of rats, to measure the contents of serum amylase (AMS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), The expression levels of TLR4, MyD88, IRAK-4 and IRAK-4 were detected by RT-PCR, Westen Blot and IHC, and the contents of IL-2, iNOS and IFN-γ were detected by ELISA. Results (1) Compared with the sham operation group, the rats in the AP model observation group had a relatively poor general survival condition, a significant increase in serum amylase (AMS), alanine aminotransferase (ALT), glutamic oxaloacetase (AST). Under the microscope, the pancreatic tissue structure was scattered, necrosis and congestion were serious. The expression levels of TLR4, MyD88, IRAK-2 and IRAK-4 gene protein in pancreatic tissue were significantly increased, and the contents of IL-2, iNOS and IFN-γ in pancreatic tissue homogenate were significantly increased (P< 0. 05). (2) After intervention, the general living conditions of the rats in the treatment group were improved in different degrees, serum amylase (AMS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were decreased, interstitial edema and necrotic foci were significantly improved under the microscope, the expression levels of TLR4, MyD88, irak-2 and IRAK-4 gene protein in pancreatic tissue were decreased, and the contents of IL-2, iNOS and IFN-γ in pancreatic tissue homogenate were decreased, especially in the large dose group of Dahuang Mudan decoction, the difference was statistically significant (P< 0. 05). Conclusions Dahuang Mudan decoction can improve pancreatic injury in rats with acute pancreatitis, and its mechanism may be related to the inhibition of TLR4 / MyD88 signaling pathway.