Objective: To observe the expression of HIF-1α in cerebral hypoxia rats and the effect by ginsenoside Rd interference as well as to explore its possible mechanism. Methods: 50 adult wistar rats were divided into 4 groups: normal oxygen control group, acute hypoxia group, hypoxia pretreatment group and ginsenoside Rd interference group; to observe the change of hippocampus cell shape and the expression of HIF-1α in every group. Results: At immediate reoxygen time, we can found a few expression of HIF-1α protein which mostly consisted in hippocampus cell, much of them in cytoplasm; as time processed, the expression level of HIF-1α reached the peak at reoxygen 4h; the expression level of HIF-1α markedly decreased at reoxygen 9h, there is statistical differences for AOD values between control group and interference groups. (P =0.009<0.05); there is no statistical differences between two interference groups(P>0.05). Conclusion: Acute hypoxia can cause the expression of HIF-1α in rat hippocampus cells and its expression has time dependence; at the same time, hypoxia pretreatment and ginsenoside Rd interference can make the expression of HIF-1α decreased; the regulation of Ca2+ influx and the inhibition of oxygen free radicals may be one of its mechanism; it suggested that these pretreatment measures may have protective action for acute hypoxia cerebral injury, the concrete mechanism still to be clarified.