ObjectiveTo observe the effect and mechanism of curcumin on cognitive function in the mouse model of low oxygen-induced chronic nerve injury. MethodEighty male C57BL/6 mice were randomized into eight groups： control， low-， medium-， and high-dose （100， 200， and 300 mg·kg^-1， respectively） curcumin， model， model + low-dose curcumin， model + medium-dose curcumin， and model + high-dose curcumin groups （n=10）. The mouse model of low oxygen-induced nerve injury was prepared by continuous stimulation with simulated oxygen concentration at Lhasa altitude （13% O₂ at about 3 700 m） for 14 days. After the completion of modeling， mice in the six curcumin groups were administrated with curcumin at corresponding doses by gavage， while those in the control group and the model group were administrated with the same amount of normal saline once a day for one week. After that， open field， novel object recognition， and Morris water maze tests were carried out to reveal the behavioral changes of mice. The morphological changes of the hippocampus were observed by hematoxylin-eosin staining. The mRNA levels of interleukin （IL）-6 and tumor necrosis factor （TNF）-α in the hippocampus and peripheral blood of mice were determined by real-time PCR. The activation of microglia in the hippocampus was observed by Iba-1 staining. The protein levels of brain-derived neurotrophic factor （BDNF） and cAMP-response element-binding protein （CREB） in the hippocampus were determined by Western blot. ResultCompared with the control group， the model group showed decreased new object recognition rate （P<0.01）， extended time to find the platform （P<0.01）， and reduced platform crossings （P<0.05）， which proved that the cognitive function of mice was impaired. Compared with model group， the model + medium-dose curcumin group showed increased new object recognition rate， shortened time to find the platform， and increased platform crossings （P<0.05，P<0.01）. Moreover， the application of curcumin repaired the abnormal morphological and structural changes in the hippocampus， reduced the inflammatory cytokine levels and activation of microglia， and upregulated the expression of CREB and BDNF （P<0.05）. ConclusionCurcumin demonstrates a therapeutic effect on low oxygen-induced cognitive decline， which provide a potential cure for treating chronic brain injury induced by high-altitude low oxygen in clinical practice.