Even though many studies have focused on the associated risk factors, pathology, therapy, prognosis for CTEPH in recent years, still there is much to be further recognized, especially for its pathogenesis. Early treatment before right heart insufficient by pulmonary endarterectomy or suitable medical treatment was crucial for prognosis improvement. This highlighted the need to develop sensitive and reliable biomarkers for early diagnosis of CTEPH. At present, possibly owing to the complex pathophysiology of CTEPH, the reported candidate molecular biomarkers for CTEPH, including asymmetric dimethylarginine, D-Dimer, heart-type fatty acid-binding protein and brain natriuretic peptide still were not sufficiently reliable for clinical application. Therefore, combination of some biomarkers representing different pathophysiological aspects of the disease might be the tendency for future biomarker screening. The emerging of microarray technology has made it possible to achieve tens of thousands of gene expression simutaneously as the base of screening. Biomarker signature have been studied in many diseases, including cancers, cardiovascular diseases. MiRNAs were recognized of limited amount to regulate most of protein-coding gene expression post-transcriptionally. Therefore, it seemed more practical to explore miRNAs as biomarkers for the diseases with complex etiology and pathophysiology. Studies on miRNA signature have increased steeply during recent few years. These studies have shown that certain miRNA signature had satisfactory efficacy for disease diagnosis and evaluation. As ideal diagnostic biomarker, miRNAs possess many sustaining properties. First, circulating miRNAs were remarkably stable even exposed to harsh environment and this characteristics made detection reproducibly. Second, the pathognostic cell Wortmannin resource of miRNAs determined the high specificity of circulating miRNAs for disease diagnosis. Third, miRNAs were small molecules that lacked post-processing modification. They could be detected by an extremely sensitive method at very low starting concentration. Although large population verification of the results in our study is still needed, circulating miRNAs provide a promising prospect for CTEPH diagnosis. During verification, the signature can be further simplified for clinical application, and the efficacy and accuracy can be enhanced. Since 2008, many studies have indicated that circulating miRNAs were functional molecules which might act in cell communication and suppress the translation of target genes in recipient cells. A recent study showed that, in healthy subjects, circulating miRNA profile was similar to the profile of circulating blood cells, but this similarity was disturbed in diseased subjects, and the circulating miRNA profile was endued with characteristics of cells involved in the disease. In this study, we observed that the differentially expressed circulating miRNAs had important regulatory function in CTEPH pathogenesis, such as remodeling of pulmonary vascular, imbalance of vascular tone or inflammation. Many of these were regarded to be involved in CTEPH etiology. However, few of them have been thoroughly interpreted.