Abstract Body: Obesity, recognized as an inflammatory disease, is a risk factor for several additional disease states, including cardiovascular disease (CVD). Prior work from our lab implicates IL-1β originating from myeloid cells in adipose tissue in regulating myelopoiesis, peripheral monocytosis, and atherosclerotic necrotic cores. Extracellular vesicles (EVs) are lipid bilayer bound structures containing proteins, nucleic acids and lipids that are released by most cell types, with the potential to mediate signaling at distant sites. We therefore hypothesized that IL-1β is secreted from macrophages of obese adipose tissue via EVs and that this IL-1β is bioactive, targeting cells in the bone marrow and atherosclerotic plaques, contributing to obesity-associated increases in myelopoiesis, monocytosis and necrotic core size. Using scRNAseq data of human obese adipose tissue, we found IL-1β expression confined to monocyte and macrophage clusters, corroborating previous murine work. Furthermore, we demonstrate that IL-1β secreted from murine obese adipose tissue was found to be predominantly in the form of extracellular vesicles (EV fraction 67.2 pg/mL ± 18.6 vs non-EV 29.0 pg/mL ± 13.4, p= 0.001, n= 7). By using western blotting and an IL-1β receptor (IL-1R) reporter cell line, we show that IL-1β transported by macrophage-derived EVs was in the bioactive, mature form and able to signal through the IL-1R on the recipient cells (IL-1β containing EVs 0.45 AU ± 0.40 vs non-IL-1β containing EVs 0.003 AU ± 0.001, p=0.032, n=4) . We are further investigating the effect of IL-1β⁺ EVs on myelopoiesis and monocytosis in vivo. In summary, obese adipose tissue macrophages secrete bioactive, EV bound IL-1β, which contributes to obesity associated with myelopoiesis, monocytosis, and atherosclerosis.