Abstract: Objective To estimate the median effective dose (ED\50) of oral administrated HX0969w, fospropofol disodium and propofol emulsion in rats, and to compare the sedative-hypnotic effects and safety of the three drugs. Methods The ED\50 of the three drugs were determined using sequential method. Thirty healthy adult Sprague-Dawley rats were divided into three groups randomly, being orally administered with HX0969w (\n=10), fospropofol disodium (\n=10) and propofol emulsion （\n=10）, respectively. The neurobehavioral performance of the rats was observed. The time of loss of forepaw righting reflex (LRR) and the time of recovery of forepaw righting reflex (RRR) were recorded. Results The ED\50 of oral HX0969w, fospropofol disodium and propofol emulsion were 96.5 mg/kg, 130.0 mg/kg and 113.8 mg/kg, respectively.HX0969w, fospropofol disodium and propofol emulsion had a mean LRR of （10.0±2.9） min,（7.5±2.8） min and （16.0±5.9） min, respectively; and a mean RRR of （66.9±21.5） min, （131.9±32.7） min and （198.9±110.0） min, respectively. Conclusion HX0969w, fospropofol disodium and propofol emulsion can produce sedative-hypnotic effects and they are safe when administered by oral route.The two propofol prodrugs HX0969w and fospropofol disodium have shorter LRR than propofol emulsion. HX0969w also has a shorter RRR than fospropofol disodium and propofol emulsion.