Objective To explore the effects and mechanism of Arglabin on neuroinflammation in mice with traumatic brain injury. Methods Male C57BL/6J adult mice were selected and randomly divided into: (1) sham operation group (Sham group), (2) sham operation + Arglabin group (Sham+Arglabin group), (3) brain injury group (TBI group), and (4) brain injury + Arglabin group (TBI+Arglabin group). Brain injury was induced by a controlled cortical impact model. After successful modeling, 5 μg/kg of Arglabin was injected intraperitoneally, once a day until the material was retrieved. Neurological function was evaluated 3 weeks after the operation; HE staining and Nissl staining were observed 4 weeks after the operation; WB detected the relative expression of NLRP3, ASC and Caspase-1 protein in brain tissues 3 days after the operation, and RT-qPCR detected the relative expression of mRNA of inflammatory factors IL-1β, IL-18, IL-6, iNOS, IL-4 and Arg1; the expression of M1 and M2 cells was observed 7 days after the operation. Results Compared with the Sham group, the nerve function of the mice in the TBI group decreased (P < 0.0001), the brain tissue damage area was significantly increased (P < 0.01), and the neurons were largely lost (P < 0.01), the expression of NLRP3, ASC and Caspase-1 proteins in brain tissue was significantly increased (P < 0.05), the expression of proinflammatory cytokines IL-1β, IL-18, IL-6 and iNOS was significantly increased (P < 0.05), the expression of antiinflammatory cytokines IL-4 and Arg1 was significantly decreased (P < 0.01), and the expression of M1 type cells was significantly increased (P < 0.01). Compared with the TBI group, the nerve function of the mice in the TBI+Arglabin group 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), the expression of NLRP3, ASC and Caspase-1 proteins in brain tissue was significantly reduced (P < 0.05), the expression of proinflammatory cytokines IL-1β, IL-18, IL-6 and iNOS was significantly reduced (P < 0.05), the expression of the antiinflammatory cytokines IL-4 and Arg1 was significantly increased (P < 0.01), and the expression of M2 type cells was significantly increased (P < 0.01). Conclusion Arglabin improves local immune microenvironment by inhibiting NLRP3 inflammasome activation to alleviate neuroinflammation in mice with traumatic brain injury.