An in vivo pilot study investigating the biocompatibility of BioGlue as a dural sealant is described. Craniotomies were performed in adult Wistar rats. After excising the dura, BioGlue was applied directly onto the cerebral cortex and sterile Surgicel (Ethicon Inc., Somerville, NJ) placed over the brain in control rats. All rats were culled 14 days post-surgery. An inflammatory cell infiltrate was found overlying the pia-arachnoid, but this did not extend into the brain parenchyma except in instances of mechanical disruption. Immunohistochemical staining for glial fibrillary acidic protein (GFAP) showed an increase in gliosis in the BioGlue treated rats but the degree of positive staining as well as the observed surface inflammation was not significant and possibly would not be clinically significant.