ABSTRACT Mesenchymal stem cells‐derived exosomes (MSCs‐EXs) applications have brought a key breakthrough in treating type 1 diabetes mellitus (T1DM) and its diabetic complications. However, various recent strategies aimed to construct prominent engineered EXs with greater precision and higher efficiency for diabetes syndrome were conducted. In this research, we seek to enhance the medicinal potentialities of MSCs‐EXs on type 1 diabetic rats' hepatic complications, via loading with either selenium (Se) or nano selenium (NSe) particles. For consecutive 4‐weeks, rats were divided into 8 groups as; control, EXs, EXs + Se, EXs + NSe, STZ‐diabetic (D), D + EXs, D + EXs + Se, and D + EXs + NSe groups. The three diabetic‐treated groups manifested a significant reduction in hepatic contents of oxidative stress (OS) (MDA, NO, and H 2 O 2 ) inflammatory (IL‐6, TNF‐α, and TGF‐β), and apoptotic (P53, BAX, caspase‐3, and Bcl2) markers, with marked elevation in hepatic antioxidant levels (GSH, GPX, SOD, and CAT). Such results were supported by the marked diminish in serum total proteins, liver function enzymes (AST, ALT, and bilirubin), and both serum and liver lipid profile fractions. In addition, hepatic histological examination showed marked improvement in liver architecture of all treated diabetic rats' groups, compared to diabetic untreated rats. Significantly, diabetic rats with EXs loaded with NSe exhibited the most therapeutic superiority.

Antioxidant and Antiapoptotic Effects of Selenium And Nano Selenium‐Loaded Exosomes on Hepatic Dysfunction of Type 1 Diabetic Rats