Objective · To observe the effect of intranasal administration of glibenclamide on the treatment of traumatic brain injury (TBI), providing new ideas for the treatment of TBI. Methods · Eight-week-old C57BL/6J mice were randomly divided into glibenclamide treatment group (n21), control group (n19) and in vivo fluorescence imaging group (n1). Glibenclamide labeled with fluorescent probe was injected into the nose of mice in the in vivo fluorescence imaging group to observe the transportation of glibenclamide into the brain. The TBI model was established in the right hemisphere of mobrain of the glibenclamide treatment group and the control groupthe controlled cortical impact (CCI) method. The mice in the glibenclamide treatment group received intranasal delivery of the drug after TBI induction, while the mice in the control group received equal doses of the solvent without glibenclamide under the same conditions. Mice were decapitated after 24 h of successful modeling. The degree of brain edema in the two groups was measuredthe percentage change in water content of brain tissues. The volume of brain damage in the two groups was measured2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The neurological function of the two groups was evaluatedrotarod test. Results · In vivo fluorescence imaging experiment showed that glibenclamide successfully reached the brain after intranasal administration. The degree of brain edema and the volume of brain damage in the control group were significantly larger than those in the glibenclamide treatment group (both PConclusion · Intranasal delivery of glibenclamide can significantly reduce TBI-caused brain edema and brain damage volume, suggesting that the drug has a certain neuroprotective effect on TBI.