Objective To investigate the effect of combination of Ligusticum chuanxiong active substance ethyl ferulate （EFE） and aerobic exercise （AE） on cognitive function of rats with Alzheimer’s disease （AD）.Methods Seventy SD rats were randomly divided into 5 groups （Control group， Model group， AE group， EFE group and AE+EFE group n=12）. The rat model of AD was induced by injecting β-amyloid 1-42 （Aβ1-42） into the hippocampus of rats on both sides. One week after modeling， the rats in AE group and AE+EFE group took aerobic treadmill exercise， while the other groups did not exercise. And the rats in EFE group and AE+EFE group were gavaged with 2 mL 100 mg/kg ethyl ferulate， the rats in other groups were gavaged with 2 mL 0.5% sodium carboxymethyl cellulose. All groups were treated for 6 weeks. After administration， the rats’ cognitive function was assessed by the Morris Water maze test. The levels of superoxide dismutase （SOD）， catalase （CAT） and malondialdehyde （MDA） in hippocampal tissue were detected according to the instructions of the kit. Hippocampal β-amyloid precursor protein lyase 1 （BACE1）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nuclear factor erythrocyte 2-associated factor 2 （Nrf2）， Kelch-like ECH-associated protein 1 （Keap1） and heme oxygenase 1 （HO-1） transcription levels were detected by qRT-PCR. The expression levels of BACE1 and Aβ1-42 in hippocampus were detected by western blot.Results Compared with AE group and EFE group， the escape latency of AE+EFE group decreased， and the number of crossing the platform within 60 s increased significantly （P<0.05）. Compared with AE group and EFE group， SOD and CAT levels in the hippocampus of AE+EFE group increased， while MDA levels in the hippocampus decreased significantly （P<0.05）. Compared with AE and EFE groups， the mRNA relative expressions of TNF-α， IL-1β and IL-6 in hippocampus of AE+EFE group decreased significantly （P<0.05）. Compared with AE and EFE groups， the relative expression levels of Nrf2 and HO-1 mRNA in the hippocampus of AE+EFE group were increased， while the relative expression levels of Keap1 mRNA decreased significantly （P<0.05）. Compared with AE and EFE groups， the relative expressions of BACE1 mRNA， BACE1 protein and Aβ1-42 protein in the hippocampus of AE+EFE group decreased significantly （P<0.05）.Conclusion Ethyl ferulate combined with aerobic exercise can effectively improve the cognitive function of AD rats， and the mechanism may be related to the inhibition of oxidative stress， inflammation and accumulation of Aβ.