The research is aimed to explore the distinct molecular signatures in discriminating the rheumatoid arthritis patients with traditional Chinese medicine (TCM) cold pattern and heat pattern. Twenty patients with typical TCM cold pattern and heat pattern were included. Microarray technology was used to reveal gene expression profiles in CD4+ T cells. The signal intensity of each expressed gene was globally normalized using the R statistics program. The ratio of cold pattern to heat pattern in patients with RA at more or less than 1:2 was taken as the differential gene expression criteria. Protein-protein interaction information for these genes from databases was searched, and the highly connected regions were detected by IPCA algorithm. The significant pathways were extracted from these subnetworks by Biological Network Gene Ontology tool. Twenty-nine genes differentially regulated between cold pattern and heat pattern were found. Among them, 7 genes were expressed significantly more in cold pattern. Biological network of protein-protein interaction information for these significant genes were searched and four highly connected regions were detected by IPCA algorithm to infer significant complexes or pathways in the biological network. Particularly, the cold pattern was related to Toll-like receptor signaling pathway. The following related pathways in heat pattern were included: Calcium signaling pathway; cell adhesion molecules; PPAR signaling pathway; fatty acid metabolism. These results suggest that better knowledge of the main biological processes involved at a given pattern in TCM might help to choose the most appropriate treatment.