Abstract: The medication rules of high frequency herb-pairs containing Codonopsis pilosula (Dangshen) were analyzed with data mining tools, and the molecular mechanisms of these herb-pairs on the gastrointestinal diseases were predicted with the network pharmacology. The R language association rules were used to mine the high frequency herb-pairs from TCM formulae containing Dangshen, and these herb-pairs would be screened out, which satisfied the following requirements with support ≥ 0.3 and confidence ≥ 0.9 at the same time. Using the Integrated Pharmacology Platform of Traditional Chinese Medicine (TCMIP) to predict the key core targets of the high frequency herb-pairs, the network of Chinese medicine-compound-target-pathway related to Dangshen were built to explore the preventing and treating molecular mechanism on gastrointestinal diseases. At last, the relation of the main active components from Dangshen and its herbal pairs with target proteins were validated by Systems Dock Web Site. The 185 formulae were selected from 543 formulae containing Dangshen, and 6 herbal pairs with Dangshen, which includes Angelica (Danggui), Licorice (Gancao), Atractylodes macrocephala (Baizhu), Poria cocos (Fuling), dried tangerine peel (Chenpi) and Astragalus membranaceus (Huangqi), were discovered with Apriori algorithm. The combination of 6 herbal pairs is similar to Bu Zhong Yi Qi Decoction; 6 herbal pairs with Dangshen were related to the target of POMC, OPRM1, CCR9 and HTR2C in TCMIP. The known targets (HTR2C, POMC, OPRM1, CCR9, OPRD1) and potential drug-targets (GNB1, GCK, SDHD, SLC25A2, DHRS4) for gastrointestinal diseases were predicted about the high frequency pairs with Dangshen. The results of GO enrichment analysis showed that the biological function was mainly located in the mitochondria and myelin sheath, and involved in the biological processes of three carboxylic acid cycle, platelet activation, and aspartic acid metabolism. KEGG pathway enrichment analysis showed that the main metabolic pathways related with Dangshen pairs involved amino acid metabolism, energy metabolism and endocrine metabolism. The prediction results showed many targets of the frequency herbal pairs with Dangshen preventing and treating gastrointestinal diseases were related with nerve cells. These herbal pairs could prevent and treat the gastrointestinal diseases through the neuroendocrine system and the brain gut axis.