We have previously demonstrated that angiotensin converting enzyme 2 (ACE2) could boost the therapeutic effects of endothelial progenitor cell (EPCs) on ischemic stroke. Here, we tested whether ACE2 could enhance the effects of EPC derived exosomes (EXs) on intracerebral hemorrhagic stroke (ICH). A bolus of EPC-EXs or ACE2-EPC-EXs (1 x 1011EXs/100 ul) labeled with PKH26 was intravenously administrated to ICH mice (C57BL/6) 24 hrs after collagenase (VII-S; 0.075 U/0.5 μl) injection. ACE2 blocker, DCX 600 was used to verify the effects of ACE2. The neurological deficit score (NDS), hemorrhage volume, brain water content, and blood brain barrier (BBB) permeability were measured at day 24 hrs after injection. The levels of ACE2, inflammatory factors in the brain were measured. We found (table): 1) Both EPC-EXs and ACE2-EPC-EXs were dominantly uptaken by the brain endothelial cells, neurons and astrocytes in peri-infarct area; 2) ACE2-EPC-EXswere more effective than EPC-EXs in decreasing hemorrhage volume, brain edema, BBB permeability and improving NDS; 3) As compared to EPC-EXs, ACE2-EPC-EXs resulted in an up-regulation of ACE2, and more down-regulated TNF-α, NFкB, IκBα expressions. 4) DCX 600 could block the protective effects of ACE2-EPC-EXs. The data suggest that infusion of ACE2-EPC-EXsexhibited protective role for anti-inflammatory effect of ACE2 mediating TNF-α/NFкB in mice after ICH.