Objective To investigate the effect of Osthole on memory function of sleep deprivation(SD) mice. Methods Forty-eight male mice were randomly divided into 4 groups;normal control group(NC group ), large platform control group(TC group),sleep deprivation group(M group)and Osthole group(Ost group). The model of SD in mice was estabished by using improved multi platform method. The ability of learning and memory was tested by using Morris water maze test and pathological changes of hippocampal neurons in mice were observed by HE staining. The serum,hippcampus malondialdehyde(MDA)contents and superoxide dismutase(SOD)activity, so as the hippocampus No content,were detected. Results Compared with NC group and TC group,the escape la-tency of M group increased significiantly and the number of crossing platform decreased significantly. There were in-creased levels hippocampus tissue,serum MDA level,hippocampal SOD activity and NO content. After supplemen-tation of Osthole,the escape latency significantly shortened in mice. The number of crossing platform was increased while the contents of MDA both in hippocampus and serum were decreased,and the SOD activity in hippocampus re-turned to normal. However,the level of NO in hippocampus was not decreased. Conclusion Osthole can protect the memory function of SD mice by reducing the the damage of hippocampal neurons through antioxidant stress.