〔Abstract〕 Objective To study the protective effect and mechanism of remimazolam on cognitive function in septic mice. Methods Fifty-four C57BL/6 mice were randomly divided into saline group(NS group),simple remimazolam group(RM group),sepsis model group[lipopolysaccharide(LPS)group] and sepsis groups with different doses of remimazolam injection(RM10,RM15and RM20groups).The sepsis model was established by intraperitoneal injection of 1 mg/kg LPS;the RM group was injected intraperitoneally with 15 mg/kg remimazolam solution; the RM10,RM15and RM20groups were respectively injected with 10,15 and 20 mg/kg remimazolam solution 30 mins before LPS injection.The number of times the mice crossed the platform and the percentage of time they stayed in the first quadrant were recorded in the Morris water maze experiment; the levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in peripheral blood and hippocampus were measured by enzyme-linked immunosorbent assay(ELISA);the levels of malondialdehyde(MDA),glutathione(GSH) and superoxide dismutase(SOD) activity in hippocampus were measured by chemical colorimetric assay; and the pathological changes of neurons in CA1 area of hippocampus were observed by Hematoxylin-eosin(HE) staining. Results In the LPS group, the number of platform crossing times, the percentage of staying time in the first quadrant, GSH level and SOD activity significantly decreased, and TNF-α,IL-1β and MDA levels significantly increased.In addition, the arrangement of neurons in CA1 area of hippocampus was disturbed; cytoplasmic staining was deepened; and the nucleus was solidly stained.Comparing RM10,RM15and RM20groups with the LPS group, the number of platform crossing times, the staying time in the first quadrant, GSH level and SOD activity increased, and the levels of TNF-α,IL-1β and MDA decreased.And the results of hippocampal staining showed a decrease in degenerated neuronal cells.When it came to the comparision in the groups with different doses of remimazolam injection, septic mice in the RM20group showed less improvement in cognitive dysfunction and inflammatory oxidative stress than the RM10and RM15groups. Conclusion Remimazolam has a protective effect on cognitive dysfunction in septic mice, and its mechanism may be related to its binding of translocator protein(TSPO) to inhibit macrophage polarization and thus reduce neuroinflammation and oxidative stress damage.It also reflects that dose of 10 mg/kg and 15 mg/kg has more significant protective effect than that of 20 mg/kg.