Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive lung degenerative disease of unknown aetiology and represents the most frequent interstitial lung disease (ILD). The diagnosis is usually made in the fourth to seventh decade (between 40 and 70 years of age) of life and males are more affected than females with a M:F ratio of 2/1 [
1]; this datum is in all likelihood influenced by the higher prevalence of smokers in the male population in comparison with females [
2,
3]. Indeed, considering well-known risk factors of IPF, apart from the genetic ones, like pathogenic gene variants in
TERT,
TERC,
SFTPC and
SFTPA [
4], the most relevant is the smoking habit, estimated by the
pack years index. Other factors, like metal, stone or wood dust, chemotherapeutic drugs and silica exposure, are more infrequent [
5,
6]. The diagnosis of IPF is reached through clinical, radiographic and, if needed, histological examination [
7]. The prognosis of the disease is poor: the overall survival is approximately only 3–5 years following diagnosis [
8]. In this complex framework, MicroRNAs (miRNAs) are thought to play a role, as it has been ascertained their function in post-transcriptional regulation. In particular, miRNAs expression studies have shown that a down-regulation in let-7d and miR-26a may have a central role in the IPF pathology onset and progression [
9]. In particular, miR-26a function is to down-regulate the expression of Lin28B, an RNA-binding protein, which functions as a silencer of let-7d. As a consequence, let-7d is prevented from its physiological action of inhibiting HGMA2, an oncogenic driver protein [
10] and a direct enhancer of the expression of TGF-β1 [
9], well known as the most important factor for epithelial-mesenchymal transition (EMT) of alveolar epithelial cells-type II (AEC-II) and, therefore, fibrosis. Other transduction pathways are considered to be involved in the pathogenesis of IPF, such as MNT (MAX network transcriptional repressor) and Smad7, suggesting that an up-regulation of these miRNAs, mir-16 and miR-210, may have a pathological role [
11,
12]. Among cell-to-cell communication strategies there is the excretion of extracellular vesicles, called exosomes, that deliver lipid, protein and genetic material (including miRNA) cargo. Several studies have shown the presence of exosomes in all the body fluids and have demonstrated the alteration of these vesicles content in pathological conditions [
13‐
17]. Therefore, exosomes could be excellent diagnostic, progression, recurrence and therapy follow-up biomarkers. Recently, a lower level of antifibrotic miRNA, like miR-141, and a higher level of profibrotic miRNA, like miR-7, have been detected in serum exosomes of IPF patients. Besides that, the same study has shown a direct relationship between the up-regulation of miR-7 and disease severity [
18].