In traditional Chinese medicine (TCM), blood stasis syndrome (BSS) is mainly manifested by the increase of blood viscosity, platelet adhesion rate and aggregation, and the change of microcirculation, resulting in vascular endothelial injury. It is an important factor in the development of diabetes mellitus (DM). According to the differences in the internal and external environment of the individual disease, BSS were divided into qi-deficiency and blood stasis syndrome (QDBS), qi-stagnation and blood stasis syndrome (QSBS), cold-coagulation and blood stasis syndrome (CCBS), heat-accumulation and blood stasis syndrome (HABS). The aim of this study was to screen out the potential candidate mRNAs in DM patients with BSS by high-throughput sequencing (HTS) and bioinformatics analysis. CRL-1730 human umbilical vein endothelial cells (HUVECs) were incubated with 10% human serum to establish models of DM with BSS, DM without BSS (NBS) and normal control (NC). Total RNA of each sample was extracted and sequenced by the Hiseq2000 platform. Differentially expressed mRNAs (DE-mRNAs) were screened between samples. On the basis of mRNA expression profiles, four comparisons were made, including QDBS vs NBS and NC, QSBS vs NBS and NC, CCBS vs NBS and NC, HABS vs NBS and NC. Then, comparisons with P values <0.05 (Fisher''s exact test), false discovery rates (FDR) <0.01 and |log2 ratios|=1 were considered as DE-mRNAs in BSS. This study screened out the DE-mRNAs in DM patients with BSS by HTS and bioinformatics analysis. Overall design: Bioinformatics analysis of transcriptome in DM patients with BSS by establishing cell models of DM with BSS.