Background Asthma is a heterogeneous chronic inflammatory disease in which several endotypes contribute to define clinical inflammatory phenotypes. MicroRNAs (miRNAs) are small non-coding RNA that regulate gene expression at the post-transcriptional level. MiRNAs appear to play a role in several physiological and pathological processes, such as development, differentiation, cell proliferation and apoptosis. These features make miRNAs potential novel biomarkers for a chronic and heterogeneous disease like asthma. Exosomes are extracellular vesicles (EVs) that contain proteins, lipids and nucleic acids, including miRNAs able to provide significant information both on physiological and pathological conditions. Several studies have shown their functional relevance in asthma. The aim of this study was to evaluate the expression of selective miRNAs from serum-derived exosome in severe and mild-to-moderate asthmatic patients compared with healthy controls. Methods MiRNAs were purified from serum exosomes and selective miRNAs (miR-21, miR-223 and Let-7a) expression levels were determined by using qRT-PCR.  For statistical analysis were used either ANOVA test, Kruskal-Wallis test, Mann-Whitney test and t-test, based on data normality. Results The levels of miR-21 were lower both in severe and mild-to-moderate asthma compared to controls (p=0.01, p=0.04). MiR-223 indeed, seemed lower in mild-to-moderate asthmatic patients than controls. No significative differences were found in Let-7a expression. Conclusions This study identified two exosome-derived miRNAs involved in asthma pathogenesis and development underlining that these may be considered useful biomarkers and promising target of future therapies.