Objective To explore the medication rule of traditional Chinese medicine in the treatment of acute pancreatitis based on data mining and network pharmacology, and to explore the mechanism of core medicine in the treatment of acute pancreatitis. Methods The prescriptions of patients with acute pancreatitis who were hospitalized in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from January 1, 2020 to December 31, 2020 were searched, and the prescription database was established to analyze the medication frequency, association rules and cluster analysis. The drug pair common target, interaction relationship and enrichment pathways were analyzed by relevant databases and software. Results A total of 238 Chinese medicine prescriptions were screened, involving 164 traditional Chinese medicines. The most frequent drug was bupleurum, and the core drug pair Radix Bupleuri- Scutellariae-Rhubarb with the highest confidence was obtained. 49 active components and 185 target genes were obtained by searching Radix Bupleuri, Scutellaria and Rhubarb. 576 targets were searched for acute pancreatitis, and 71 common targets were searched for drug pair disease. According to the degree value, the core targets were AKT1, TNF, IL-6, MAPK1, etc. Through Go and KEGG enrichment analysis, we found that the mechanism of core drugs in the treatment of acute pancreatitis is mainly related to the negative regulation of apoptotic process, positive regulation of transcription from RNA polymerase II promoter, and PI3K-Akt signaling pathway. Conclusion Radix Bupleuri- Scutellariae-Rhubarb plays a role in the treatment of acute pancreatitis through multiple targets and pathways, which provides a new idea for the clinical treatment of acute pancreatitis with traditional Chinese medicine.