Sepsis is one of the most common reasons for mortality in Intensive Care Units. As a common but severe neurological complication, sepsis associated encephalopathy (SAE) has always been ignored and there is no generally accepted treatment. In this study, we demonstrated that Mdivi-1 ameliorated brain damage assessed by Nissl staining. Furthermore, Mdivi-1 reduced TUNEL-positive cells in hippocampus, and inhibited 5100 calcium binding protein B (S100B) and neuron-specific enolase (NSE) release into plasma. Biochemical analysis also showed that Mdivi-1 protected hippocampus from oxidative stresses. Western blot analysis revealed that Mdivi-1, as a Drpl inhibitor, inhibited LPS induced dynamin-related GTPase (Drpl) increase. Interestingly, it can also attenuate LPS induced optic atrophy 1 (OPA1) and phosphorylated Drpl (p-Drpl) decrease. Thus Mdivi-1 protected rats from SAE, and this protective effect could be associated with its inhibition of Drpl and its activation of p-Drpl and OPA1. Mitochondrial dynamics may be a potential pharmacological therapeutic target for treating SAE. (C) 2018 Elsevier Inc. All rights reserved.