Fangji Huangqi Tang (FHT) is a classical formula widely used in Chinese clinical practice. In this study, a creative application of FHT for inflammation has been identified by network pharmacology-based framework. Specifically, a total of 17 bioactive compounds including 42 potential targets of FHT, and 205 related targets involved in inflammation were retrieved from mainstream databases and subjected to network analysis. 13 intersection targets indicated the principal elements linked to inflammation therapy. Top terms of Gene Ontology (GO) analysis were identified, while 7 related signaling pathways were revealed by Kyoto Encyclopedia of Genes and Genomes (KEGG) results. Subsequently, Calycosin-PTGS2 with tight binding affinity (BA) was manifested by molecular docking as the critical compound-target couple. Meaningful links between Calycosin and inflammation were implied through Arrowsmith, which overlapped with the findings in enrichment analysis, such as MAPK, NF-κB that could be regulators of PTGS2. In summary, the present study explored the potential targets and signaling pathways of FHT against inflammation, which may help to illustrate the mechanisms responsible for the action of FHT and provide a better understanding of its anti-inflammatory effects.