Rosi treatment of obese mice induces major changes in adipose tissue macrophage (ATM) transcriptomes, promoting anti-inflammatory polarization and reducing pro-inflammatory polarization. Rosi-treated ATMs secrete miRNA-containing extracellular vesicles (sEVs) that improve insulin sensitivity and glucose homeostasis in vivo and in vitro. These sEVs, particularly those containing miR-690, enhance insulin sensitivity in adipocytes, myotubes, and hepatocytes. Rosi-ATM-sEVs rescue obesity-induced glucose intolerance and insulin resistance without the typical side effects of weight gain or hemodilution. The beneficial effects are mediated by miR-690, which enhances insulin sensitivity and glucose-stimulated insulin secretion (GSIS). miR-690 is upregulated in Rosi-treated ATMs and is essential for the metabolic effects of Rosi-ATM-sEVs. In vivo studies show that miR-690 antagomir treatment blocks the beneficial effects of Rosi-ATM-sEVs, confirming miR-690's role in mediating insulin sensitivity. These findings suggest that ATM-sEVs, particularly those enriched with miR-690, could serve as a therapeutic approach to improve insulin sensitivity without the adverse effects of traditional thiazolidinediones.Rosi treatment of obese mice induces major changes in adipose tissue macrophage (ATM) transcriptomes, promoting anti-inflammatory polarization and reducing pro-inflammatory polarization. Rosi-treated ATMs secrete miRNA-containing extracellular vesicles (sEVs) that improve insulin sensitivity and glucose homeostasis in vivo and in vitro. These sEVs, particularly those containing miR-690, enhance insulin sensitivity in adipocytes, myotubes, and hepatocytes. Rosi-ATM-sEVs rescue obesity-induced glucose intolerance and insulin resistance without the typical side effects of weight gain or hemodilution. The beneficial effects are mediated by miR-690, which enhances insulin sensitivity and glucose-stimulated insulin secretion (GSIS). miR-690 is upregulated in Rosi-treated ATMs and is essential for the metabolic effects of Rosi-ATM-sEVs. In vivo studies show that miR-690 antagomir treatment blocks the beneficial effects of Rosi-ATM-sEVs, confirming miR-690's role in mediating insulin sensitivity. These findings suggest that ATM-sEVs, particularly those enriched with miR-690, could serve as a therapeutic approach to improve insulin sensitivity without the adverse effects of traditional thiazolidinediones.