Abstract: To provide basic research data for astronauts to take medicine reasonably and safely,some pharmacokinetic studies on promethazine and ephedrine were carried out in rats' plasma to obtain the pharmacokinetic parameters in different simulated weightlessness periods.A rat tail-suspension model was used to simulate weightlessness,and an HPLC-MS/MS method was developed to determine the promethazine and ephedrine quantification in rat plasma.The pharmacokinetic parameters in simulated weightless group show the differences between control and model groups,such as the area under the concentration-time curve (<i<A</i<<sub<UC0-<i<t</i<</sub<),peak plasma concentration (<i<C</i<<sub<max</sub<),elimination rate constant <i<K</i<<sub<e</sub< and half-life (<i<T</i<<sub<1/2</sub<).Different simulated weightlessness periods have a significant impact on the pharmacokinetic process of drugs in rats.