Aim To explore the molecular mechanism of Radix Salviae on atherosclerosis based on the network pharmacology. Methods Radix Salviae’s active compounds were collected from reference and traditional Chinese Medicine databases, and put into PharmMapper to get their potential targets. Then KEGG-pathway analysis and GO enrichment analysis were made by DAVID database. Finally the network was drawn and analyzed by Cytoscape with information above. Results Sixteen compounds of THP acquired 344 compound targets which also got 6 atherosclerosis-related pathways and 28 biological processes. The biological processes can be divided into four modules—protection of endothelial cell function, antioxidant, anti-atherosclerotic plaque formation, conditioning blood lipid levels. Conclusion These findings reflect the molecular mechanism of Radix Salviae on atherosclerosis. It provides not only a theoretical basis for the study of Radix Salviae on atherosclerosis, but also a new paradigm for the study of the mechanism of traditional Chinese medicine such as Radix Salviae.