Aims: Lung epithelial cells are the first line of defence against external stimuli potentially dangerous to the lung. These cells interact macrophages. We focused our attention on the flame retardant PBDE-47?s effects on cell-cell communication between macrophages and lung epithelial cells by mean of small Extracellular Vesicles (sEVs). Methods: sEVs from M(LPS) THP-1 macrophage-like cells after PBDE-47 treatment (sEVsPBDE+LPS) were characterized by Nanoparticle Tracking Analysis and their microRNA cargo studied by Real Time PCR. Confocal microscopy was applied to study sEVs cellular uptake by A549 cells. The expression of TJs, adhesion molecules, inflammation markers and mucus production in A549 culture in ALI conditions was studied by Real Time PCR and confocal microscopy. Results: sEVs microRNA cargo analysis showed that PBDE-47 modulated the expression of the miR-15a-5p, miR29a-3p, miR-143-3p and miR-122-5p. Furthermore, A549 cells cultured in ALI conditions incubated with sEVsPBDE+LPS showed that ZO-1, Claudin, E-cadherin and Vimentin mRNAs were increased in A549 cells after sEVsPBDE+LPS treatment. Indeed, IL-8 and mucins (MUC5AC and MUC5B) mRNA expression were up- and down-regulated, respectively. Conclusions: Our data indicate that macrophages exposed to PBDE-47 might affect the normal function of the lung epithelium by altering the miRNA cargo of macrophage-derived sEVs, affecting the mRNA expression of TJs, adhesion molecules, cytokines and EMT markers and, potentially, contributing to the development of cancer in the lung.