Objective: To simulate and explore the synergistic mechanisms between Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos of Danhong injection using computer systems biology approach. Method: The combined TCMGeneDIT database and Agilent literature search (ALS) system was used to dig the protein information of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos. The protein interaction networks were respectively built based on the protein-protein interaction extracted from the BIND

BioGRID database. The differences and similarities of the networks were compared via difference and intersection module of the Merge programme. Result: There were 934 proteins contained in the common highly-connected protein network of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos. Four subnetworks were extracted from the common highly-connected protein network with significant difference (P<0.05) using clusterONE. Gene ontology cluster analysis demonstrated the functions of common highly-connected protein network were associated with 4 biological processes

including RNA metabolic process

nuclear factor kappa B(NF-κB) cascade

lipid homeostasis

Rho protein

Rho protein and small GTPase mediated signal transduction. The 1 431 difference protein networks extracted from the difference module analysis between Danhong injection protein and common highly-connected protein network had the relationship with the cell proliferation

migration and autophagy. Conclusion: The computer system biology approach simulated and explored the synergistic mechanisms between Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos of Danhong injection. The mechanisms might be related to the RNA metabolic process

NF-κB cascade

cell proliferation

migration and autophagy.