Objective：To investigate the protective effects of propofol derivative cqmu-039 on cerebral ischemia-reperfusion injury in SD rats and its mechanisms. Methods：A total of 40 SD rats were randomly divided into 5 groups：sham surgery group，cerebral is－chemia-reperfusion（IR） model group，low（6 mg/kg），medium（12 mg/kg） and high（24 mg/kg） doses of cqmu-039 groups. IR model was generated via the surgery of middle cerebral artery occlusion（MCAO） for 2 h and then reperfusion of blood for 24 h. Sham surgery was performed in the same way as IR model without implanting the embolus. Three different doses of cqmu-039 were injected imme－diately after the IR surgery was performed. Protective effects of cqmu-039 were evaluated through the neurological behavioral score，2，3，5-triphenyltetrazolium chloride（TTC） staining and expressions of glial cell derived neurotrophic factor（GDNF） and glial fibril－lary acidic protein（GFAP） in the hippocampus. Results：Neuronal injury was significantly improved in cqmu-039 groups than in model group. In addition，lower neurological behavioral scores，smaller cerebral infarct size and higher expressions of GDNF in CA1，CA3 and cortex regions were observed in cqmu-039 groups than in model group（P<0.05，P<0.01，P<0.01）. Expressions of GFAP in CA1，CA3 and dentate gyrus regions in cqmu-039 groups were decreasent in a dose-dependent manner. Conclusions：Propofol deriva－tive cqmu-039 can effectively improve cerebral ischemia-reperfusion injury of rats through increasing expressions of GDNF and de－creasing expressions of GFAP.