〔Abstract〕 Objective To investigate the effects of high glucose-stimulated macrophage-derived exosomes on TGF-β1/Smad3 pathway in kidney tissues of C57 mice. Methods Macrophage-derived exosomes were injected into male SPF-class C57 BL/6 mice via the tail vein. The animals were divided into three groups: high glucose-stimulated macrophage-derived exosomes( HG-Exo),mannitol-stimulated macrophages-derived exosomes( MC-Exo),and normal glucose-stimulated macrophage-derived exosomes group( NG-Exo). The urine and kidney tissues of mice were collected after 8 weeks. The urinary protein excretion rate was detected by the urinary albumin kit. The proliferation of mesangial cells and the degree of matrix expansionwas observed by HE staining and PAS staining. The infiltration of macrophages CD68 and the expression of extracellular matrix,including collagen-Ⅳ( Col-Ⅳ) and fibronectin( FN),in renal tissues were detected by immunohistochemistry. The expression of inflammatory factors TNF-α,IL-1β and extracellular matrix α-Smooth muscle actin( α-SMA),Col-Ⅳ,FN and TGF-β1/Smad3 proteins in kidney tissues were detected by Western blot. Results It showed that the proliferation of mesangium in HG-Exo group was significantly higher than that in NG-Exo group and MC-Exo group by HE and PAS staining,and the expression of CD68,Col-Ⅳ and FN in renal tissue were also higher in the HG-Exo group by immunohistochemistry stain. The expression of inflammatory factors such as TNF-α,pro-IL-1β,IL-1β and extracellular matrix including α-SMA,Col-IV,FN and TGF-β1,Smad3 and p-Smad3 in HG-Exo group were higher than those in NG-Exo group and MC-Exo group by Western blot. Conclusion High glucose-stimulated macrophage-derived exosomes can cause inflammation and extracellular matrix in mouse kidney tissue,and its mechanism may be related toactivation of TGF-β1/Smad3 signaling pathway.