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Results: Fecal Enterobacteriaceae counts, plasma lipopolysaccharide (LPS) levels, and intestinal permeability were higher in db/db than in db/+ mice, which were reduced by oral administration of a non-absorbable antibiotic, polymyxin B (PL-B), in db/db mice without changing their plasma glucose levels. The infarct volume, blood-brain barrier permeability, and microglia counts at the ischemic zone border, were higher and the neurological severity scores were worse in db/db than in db/+ mice at 24 hours after transient middle cerebral artery occlusion. In contrast, cerebral injury and neurological function were improved in db/db mice that received PL-B compared to that in those who did not. LPS and its receptor, toll-like receptor (TLR) 4, were detected in the microglia at the ischemic zone border by immunohistochemistry. LPS was more abundant and levels of TLR4, inflammatory cytokines such as interleukin-6 and …