Pronounced inflammation after intracerebral hemorrhage (ICH) contributes to secondary brain injury, which seriously affects the prognosis of ICH patients. Fractalkine (FKN)/CX3CR1 pathway may play an important role in regulating inflammatory reactions after ICH. As resident immunocyte in brain, microglia is essential for inflammatory reactions in central nervous system. This study intends to explore the effect of FKN/CX3CR1 pathway on microglia after experimental ICH and its possible mechanisms. In mouse ICH models, FKN and TGF-b1 levels gradually increased and showed a positive correlation, both of which peaked at the third day after ICH model. Compared with ICH only, the ratio of s-FKN/m-FKN, microglia activation, and neuronal apoptosis were all decreased after injecting ADAM10 inhibitor (G1254023X) into the lateral ventricle. The expression of inflammatory factors were increased after stimulation with hemin in BV2 cells. The addition of m-FKN reduced the inflammatory response to a certain extent, and the inhibitor of TGF-b1 could counteract the effect of m-FKN.In conclusion, in mouse ICH model, the expression of FKN is increased, and m-FKN may inhibit the activation of microglia and reduce neuron apoptosis by promoting the expression of TGF-b1.(c) 2020 International Hemorrhagic Stroke Association. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.