Objective To evaluate the effects of sirolimus on scopolamine-induced cognitive dysfunction in rats.Methods Thirty male Wistar rats,aged 3 months,weighing 200-250 g,were equally randomized into 3 groups:normal saline group (NS group),scopolamine group (SC group) and scopolamine + sirolimus group (SS group).Normal saline,scopolamine 0.8 mg/kg and sirolimus 3.5 mg/kg + scopolamine 0.8 mg/kg were injected intraperitoneally in groups NS,SC and SS,respectively,and the injection was continued for 14 consecutive days.The cognitive function was assessed by Morris water maze test on 15th day.After behavior test,the rats were sacrificed and the prefrontal cortex and hippocampus were harvested for determination of amyloid β protein (Aβ) and Tau protein expression.Results Compared with NS group,the escape latency was significantly prolonged,the ratio of time spent in the target quadrant was decreased,Aβ expression in prefrontal cortex and hippocampus was upregulated and Tau protein expression in prefrontal cortex and hippocampus was down-regulated in group SC (P ＜0.05 or 0.01).Compared with SC group,the escape latency was significantly shortened,the ratio of time spent in the target quadrant was increased,Aβ expression in prefrontal cortex and hippocampus was down-regulated and Tau protein expression in prefrontal cortex and hippocampus was up-regulated in group SS (P ＜ 0.05 or 0.01).Conclusion Sirolimus can significantly improve scopolamine-induced cognitive dysfunction in rats and the changes in the expression of Aβ and Tau protein in prefrontal cortex and hippocampus may be involved in the mechanism.