Orally administered Lactobacillus strains, including L. plantarum No.14 and L rhamnosus GG, reportedly reduce inflammatory cytokine production in mice. The present study tested our idea that circulating exosomes mediate the action of Lactobacillus strains. The lipopolysaccharide-induced production of TNF-alpha and IL-6 in vitro was attenuated in peritoneal exudate cells (PECs) isolated from C57BL/6N mice that had been fed L. plantarum No.14. When PECs were cultured for 24 h with exosomes isolated from the serum of mice fed L plantarum No.14 or L. rhamnosus GG, accumulation of both TNF-alpha and of the corresponding mRNA was lowered. Growth in the presence of these exosomes also decreased the production of TNF-alpha and IL-6 by the murine macrophage cell line RAW264.7. In contrast, supplementation with exosome-depleted serum of mice fed L plantarum No.14 or L. rhamnosus GG failed to affect the production of TNF-alpha and IL-6 by RAW264.7 cells. When PECs and RAW264.7 cells were cultured for 24 h with PKH67-labeled exosomes isolated from murine serum, fluorescent signal was observed inside the cells, suggesting that these cells incorporate serum exosomes. We propose that the anti-inflammatory activity of orally administered L plantarum No.14 and L rhamnosus GG is mediated, at least in part, by circulating exosomes. (C) 2017 Elsevier Inc. All rights reserved.