Objective To explore the effects and mechanism of arglabin on neuroinflammation in mice with traumatic brain injury (TBI). Methods Adult male C57BL / 6J mice were divided randomly into: sham operation (Sham), Sham + Arglabin, TBI and TBI + Arglabin groups. TBI was induced by controlled cortical impact. After successful modeling, mice received 5 μg / kg arglabin by intraperitoneal injection, once a day until the material was retrieved. Neurological function was evaluated 3 weeks after the operation. Hematoxylin-eosin(HE) and Nissl staining were performed 4 weeks after the operation. Relative protein expression levels of NLRP3, apoptosis-associated specklike protein containing a caspase-recruitment domain ( ASC), and Caspase-1 in brain tissues were detected by Western Blot 3 d after surgery, and relative mRNA levels of the inflammatory factors interleukin (IL)-1β, IL-18, IL-6, inducible nitric oxide synthase ( iNOS), IL-4, and Arg1 were detected by RT-qPCR. M1 and M2 cells were observed 7 d after the operation. Results Compared with the findings in the Sham group, in TBI group mice, nerve function was reduced (P<0. 0001), the brain-tissue damage area was significantly increased ( P<0. 01), and neurons were largely lost (P<0. 01). Additionally, NLRP3, ASC, and Caspase-1 protein levels in brain tissue were significantly increased (P<0. 05), the proinflammatory cytokines IL-1β, IL-18, IL-6, and iNOS were significantly increased (P<0. 05), and the anti-inflammatory cytokines IL-4 and Arg1 were significantly decreased (P<0. 01).Lastly, levels of M1 type cells were significantly increased ( P<0. 01). Compared with the findings in the TBI group, in the TBI + Arglabin group, nerve function was significantly improved (P<0. 01), the brain tissue-damage area was significantly reduced ( P<0. 01), neuronal loss was significantly reduced ( P<0. 01), In addition,NLRP3, ASC, and Caspase-1 proteins in brain tissue were significantly reduced (P<0. 05), the proinflammatory cytokines IL-1β, IL-18, IL-6, and iNOS were significantly reduced (P<0. 05), the anti-inflammatory cytokines IL-4 and Arg1 were significantly increased (P<0. 01), and M2 type cells were significantly increased (P<0. 01). Conclusions Arglabin improves the local immune microenvironment by inhibiting NLRP3 inflammasome activation to alleviate neuroinflammation in mice with TBI.