Abstract: OBJECTIVE To prepare an O/W type indomethacin cream and to investigate of its in vitro release. METHODS With the mass of tween 80, glycerol monostearate, liquid paraffin, petroleum jelly as the research object, centrifugal, heat-resisting and cold-resisting tests whether stratified and cream appearance as an indicator, the L₉(3⁴) orthogonal design was used to select cream prescription. Then the cumulative permeation amount of cream was determined by HPLC in the release medium. The analgesic effect of cream was observed by the method of hot plate in mice analgesic experiment. RESULTS The best prescription was Tween-80 0.45 g, glycerin monostearate 0.9 g, liquid paraffin 0.9 g, petrolatum jelly 0.6 g. Cumulative permeation amount of indomethacin cream almost equal velocity increased with time. And cream had obvious analgesic effects. CONCLUSION The cream is uniform in color, homogeneous, exquisite and easy to spread. The prescription is stable. Cumulative permeation amount of indomethacin cream has a good linear relationship with time. The method is simple and reliable.