Abstract: Objective To study the optimal preparation conditions of morphine gelatin microspheres by orthogonal design. Methods Morphine gelatin microspheres were prepared with the double emulsion method. Optimal preparation conditions were selected with orthogonal design combined with multi-index test. Mean diameter and size distribution of microspheres,drug loading and encapsulation efficiency were used as evaluating indicators. Results The morphine gelatin microspheres produced by the selected procedure were good in shape,and the mean diameter distribution conformed to the requirements. The drug loading was about 20.94% and the embedding ratio was 86.27%. Conclusion Optimization of preparation techniques for morphine gelatin microspheres can be achieved by orthogonal experiment.