Objective：To explore the neuroprotective effects and the underlying mechanisms of shikonin(SK)after traumatic brain injury(TBI). Methods：Forty C57BL/6 mice were randomly assigned to 4 groups as follows：sham operation group(Sham group)，TBI group，TBI + 1 mg/kg shikonin group(TBI+SK 1 mg/kg)，TBI + 5 mg/kg shikonin group(TBI+SK 5 mg/kg). The modified neurological severity scores(mNSS)and the apoptosis of neurons after TBI(Neuron/TUNEL)was observed，the integrity of the blood brain barrier (BBB)was detected by Evans blue staining. Moreover，we used Western blot and RT⁃PCR to determine the expression of NLRP3/ASC/ IL⁃1β/Caspase1 and detected the changes in the levels of oxidative stress markers including ROS，LPO，MDA and antioxidant enzymes which includes SOD and GPx in the edema zone around the cortical injury. The Neuro⁃2a cell line and BV2 cell line were cultured in vitro，stimulated by LPS to establish the inflammatory environment. We used Western blot to observe the inflammatory response of BV2cells and observed that the changes of neuronal apoptosis by flow cytometry. Results：Shikonin treatment improved mNSS after TBI and exerted neuroprotective effects. Shikonin could inhibit the level of ROS，LPO，MDA，and promoted the increase of SOD，GPx， alleviating the oxidative damage after TBI. Moreover，shikonin significantly inhibited the inflammatory activation of NF ⁃ κB/NLRP3 after TBI，and inhibited the activation of microglia and astrocytes in the penumbra around the injury. Conclusion：Shikonin may play a neuroprotective effect after TBI via inhibiting the activation of NF⁃κB/NLRP3 and alleviating oxidative stress.