〔Abstract〕 Objective To study the differential expression and diagnostic value of miR-26 a-5 p and miR-151 a-3 p in plasma exosomes of tuberculosis. Methods Differentially expressed miRNAs(miR-26 a-5 p and miR-151 a-3 p) in tuberculosis exosomes were identified through bioinformatics website. Furthermore, 70 tuberculosis patients(tuberculosis group) and 58 healthy subjects(healthy control group) were selected for clinical validation: Plasma exosomes, extracted by differential centrifugation, were identified by Western blot, transmission electron microscopy, nanoparticle tracking analysis.The expression levels of miR-26 a-5 p and miR-151 a-3 p in plasma exosome were detected by RT-qPCR in the tuberculosis group and the control group. The diagnostic value of miR-26 a-5 p and miR-151 a-3 p in tuberculosis was evaluated by ROC curve. Results The characteristics of exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot, which showed that plasma exosomes were extracted successfully. In clinical validation, the internal and external parameters were calibrated simultaneously, the expression level of miR-26 a-5 p in plasma exosome of patients with tuberculosis was lower than that in control group(P<0.000 1), and the expression level of miR-151 a-3 p in plasma exosome of patients with tuberculosis was higher than that in control group(P<0.000 1), which were consistent with the bioinformatics results. As a diagnostic marker, taking internal reference as the benchmark, the AUC of plasma exosome miR-26 a-5 p and miR-151 a-3 p for tuberculosis differentiation was 0.872 and 0.709, the AUC of the combined miR-26 a-5 p and miR-151 a-3 p was 0.915(P<0.000 1). Taking external reference as the benchmark, the AUC of plasma exosomes miR-26 a-5 p and miR-151 a-3 p were 0.829 and 0.854 respectively, the AUC of the combined miR-26 a-5 p and miR-151 a-3 p was 0.911(P<0.000 1). Conclusion The expression level of plasma exosome-derived miR-26 a-5 p decreases in tuberculosis patients and the expression levelof miR-151 a-3 p increases, and the clinical diagnostic efficiency of bothis high, which may be a potential biomarker for the diagnosis of tuberculosis.