Epilepsy is a neurological disorder that afflicts over 65 million people worldwide. Novel investigational antiseizure drugs (ASDs) for epilepsy are frequently evaluated in the corneal kindled mouse (CKM) model of temporal lobe epilepsy. Methylcellulose (0.5%; MC) is a commonly used vehicle for the delivery of investigational ASDs because it facilitates solubilization of hydrophobic compounds. When administered by the oral (PO) route, MC is considered an FDA “generally recognized as safe” (GRAS) compound. Though frequently used in preclinical studies, there is limited data pertaining to the tolerability of repeated intraperitoneal (IP) administration of MC. Our prior histopathology on a CKM that had received chronic IP administration of investigational ASDs delivered in MC revealed widespread accumulations of foam cells (e.g. macrophages) in the glomerular capillaries, liver sinusoids, spleen, choroid plexus, mediastinal lymph nodes, mesentery, and serosal surfaces of abdominal organs. Associated with the foam cell accumulations, there was varying attending inflammation and occasional secondary tissue necrosis. CKM may be more sensitive to MC because animals and humans with epilepsy exhibit increased sensitivity to chemical compounds, but other studies in naïve rats (i.e., without epilepsy) who had received MC via the IP route have also previously demonstrated such foam cell accumulation. Thus this study tests the hypothesis that chronic administration of IP, but not PO, MC incites lesions in both sham-kindled and CKM. Male CF-1 mice (n=3-6/group) were sham-or corneal-kindled for 4 weeks. Mice were then treated with either 0.5% MC or sterile saline, administered by the IP or PO route twice weekly for 6 weeks. Mice were longitudinally examined during the chronic dosing period by a veterinarian blinded to condition. Animals were euthanized and tissues collected for histopathology following the chronic MC administration period. This study will thus define the tolerability of chronic IP MC administration in naïve mice and in CKM.