Type 2 Diabetes Mellitus is primarily characterized by hyperglycemia accompanied by adipose tissue dysfunction. More importantly, diabetes is a risk factor for stroke and other cerebrovascular diseases, which might be related to poorly explored adipose tissue dysfunction. Even though adipose tissue is comprised of various cells, it is found that predominantly adipocyte dysfunction contributes to diabetes and related complications. Exosomes are extracellular vesicles released from almost all cells with varying functions in different conditions. Here, we aim to determine the function of adipocyte-derived exosomes (Adp-EXs) in high glucose (HG) conditions. We hypothesized that Adp-EXs from the HG group would induce cytotoxicity and oxidative stress in primary human brain microvascular endothelial cells (HBMECs). First, the level of Adp-EXs was measured after HG treatment. Secondly, their effects were studied on HBMECs after co-incubation. Adipocytes were cultured in normal glucose (NG) or HG (25mM) media to isolate Adp-EXs by serial ultracentrifugation method. The size and concentration of Adp-EXs were determined via the Nanoparticle Tracking Analysis system. Adp-EXs at three concentrations (1x10 8 , 5x10 8 and 1x10 9 particles/mL) were co-incubated with HBMECs for 24 to 48 hours to evaluate optimal cellular communication. PKH26-labelling (2uL/mL) of Adp-EX was performed to track its incorporation into HBMECs. Dihydroethidium staining and flow cytometry quantified reactive oxygen species production and cytotoxicity was determined by lactate dehydrogenase assay. For all experiments, n=5-10 and mean SEM=8.600±6.194. Results showed: 1) HG increased Adp-EX levels without size differences between NG and HG groups. 2) Adp-EXs integrated with HBMECs in a time and dose-dependent manner, more prominently in the HG group. 3) Adp-EXs from the HG group increased Dihydroethidium-positive HBMECs. 4) Adp-EXs from the HG group increased fluorescence for lactate dehydrogenase. In conclusion, the data suggest that HG could promote Adp-EX release, and trigger oxidative stress and cytotoxicity in HBMECs.