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Introduction: In the process of bone regeneration, a prominent role is played by macrophages involved in both the initial inflammation and the regeneration/vascularization phases, due to their M2 anti-inflammatory phenotype. Together with osteoclasts, they participate in the degradation of the bone matrix if the inflammatory process does not end. In this complex scenario, recently, much attention has been paid to extracellular communication mediated by nanometer-sized vesicles, with high information content, called exosomes (EVs). Considering these considerations, the purpose of the present work is to demonstrate how the presence of a pulsed electromagnetic field (PEMF) can positively affect communication through EVs., Methods: To this aim, macrophages and osteoclasts were treated in vitro with PEMF and analyzed through molecular biology analysis and by electron microscopy. Moreover, EVs produced by macrophages were characterized and used to verify their activity onto osteoclasts., Results: The results confirmed that PEMF not only reduces the inflammatory activity of macrophages and the degradative activity of osteoclasts but that the EVS produced by macrophages, obtained from PEMF treatment, positively affect osteoclasts by reducing their activity., Discussion: The co-treatment of PEMF with M2 macrophage-derived EVs (M2-EVs) decreased osteoclastogenesis to a greater degree than separate treatments., Competing Interests: Professor Shlomo Barak is the chairman of the board of Magdent Ltd. Dr Oleg Dolkart is a consultant for Magdent Ltd. The authors report no other conflicts of interest in this work., (© 2024 Trentini et al.)