Objective Microglia play dual roles after germinal matrix hemorrhage,and the neurotrophic phenotype maybe neuroprotective.However,the phenotype transformation and the way by which neuron-microglia dialogue remain unclear.We hypnotized that JWH133 triggers a neurotrophic transformation of microglia that dialogue with neuronal cells nearby via microglia derived neurotrophic factors.Methods In vivo Diffusion tensor imaging (MRI-DTI), immunohistochemistry, western blotting, proliferation detection and qRT-PCR were used to study the lone-term effects of JWH133 on the dialogue of microglia and neuronal circuit after GMH. In addition, CX3CR1 shRNA (NM_133534.1) was used to test the potential mechanism conducting neurotrophic microglia transformation.Results Long-term treatment with JWH133 by intraperitoneal (i.p.) injection promoted learning and working memories in rat pups. The drug promoted direct contact of microglia with neuronal cells by double-labelling. The FA value of DTI in the internal zone around the hematoma revealed the positive effects of JWH133 on neural restoration. Moreover, JWH133 increased brain derived neurotrophic factor (BDNF), but not minocycline, a microglia inhibitor. 3 days after JWH133 treatment, we detected reduced expression of biomarkers for neural progenitor cells (NPCs) in pups pre-injected in the lateral ventricular with CX3CR1 shRNA.Interpretation Overall, this study provides evidence that the CB2R agonist may promote a neurotrophic phenotype in microglia, beyond merely alleviating microglial proliferation and inflammation. Moreover, JWH133-induced intercellular cross-talk between microglia and neural cells may represent a novel therapeutic strategy that may be used after GMH in the future.