〔Abstract〕 Objective To investigate the effect and mechanism of exosome(Exo) transported miR-223 on brain tissue injury and microglial activation in rats with traumatic brain injury(TBI). Methods The miR-NC plasmid and miR-223 mimic plasmid were transfected into HEK293 cells by liposome method, and the expression level of miR-223 in the cells was determined by quantitative real-time PCR. Exo was extracted from transfected HEK293 cells and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot, the expression level of miR-223 in Exo was determined by quantitative real-time PCR. Forty SD rats were randomly divided into sham group, model group, NC-Exo group and miR-223-Exo group, with 10 rats in each group, TBI model was prepared by modified Feeney free fall method in all groups except sham group, rats in NC-Exo group and miR-223-Exo group were injected with cell-derived Exo transfected with miR-NC plasmid and cell-derived Exo transfected with miR-223 mimic plasmidviatail vein, respectively. Two weeks later, hematoxylin-eosin(HE) staining was used to observe the pathological changes of brain tissue in each group, Nissl staining was used to detect the changes and distribution of Nissl bodies in each group, enzyme-linked immunosorbent assay(ELISA) was used to measure the serum levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6), immunofluorescence double staining was used to observe the expression of nod-like receptor family pyrin domain containing 3(NLRP3) and ionized calcium binding adaptor molecule 1(Iba-1), Western blot was used to detect the protein expression of NLRP3, apoptosis-associated speck-like protein containing(ASC) and Caspase-1. Results After transfection, compared with control group and miR-NC group, the relative expression of miR-223 in miR-223 group significantly increased(P<0.05). The isolated particles had typical Exo morphology, the peak particle size was about 120 nm, the Exo marker proteins CD9, CD63 and CD81 were significantly overexpressed, and the relative expression of miR-223 significantly increased(P<0.05). Compared with the model group, the damage phenomenon of brain tissue in the miR-223-Exo group was improved, the morphology and number of Nissl bodies were restored, the levels of TNF-α, IL-1β and IL-6 in serum decreased(P<0.05), the intensity of NLRP3 and Iba-1 fluorescence staining in brain tissue decreased(P<0.05), the relative protein expressions of NLRP3, ASC and Caspase-1 in brain tissue were down-regulated(P<0.05). Conclusion Exo operation of miR-223 can significantly improve brain tissue injury and inhibit microglial activation in TBI rats, which may be related to the inhibition of NLRP3.