MicroRNAs (miRNAs) are a class of small noncoding RNAs, producing transcripts of about 22 nucleotides in length. miRNAs usually function as antisense regulators of other RNAs by degrading their targets. Recently, miRNAs have emerged as interesting new drug targets due to their regulatory role in essential biological processes. Salvianolic acid B (SalB) is one of the major pharmacologically active ingredients of Salvia miltiorrhiza, a traditional oriental medicine for treatment of cardiovascular disorders. In this study, we determined whether miRNAs play a role in regulation of various gene expression responses to SalB in human umbilical vein endothelial cells (HUVECs). We used the microarray approach to evaluate levels of both miRNA and mRNA, and found that 171 miRNAs were differentially expressed in SalB-treated HUVECs. We additionally identified 848 messenger RNAs (mRNAs) that are anti-correlated with the miRNAs expression. The Gene Ontology (GO) term enrichment was analyzed for identification of biological processes of target genes affected by differential expression of miRNA. Among 848 genes investigated, cardiovascular disease-related genes were selected in SalB-treated HUVECs. These results suggest that SalB may modulate miRNA and their target gene expression in order to exert vascular protective effects in human endothelial cells.