Disclosed is a method of preparing sustained release microspheres by spray-drying liquids with different compositions for preparation the sustained release microspheres through an ultrasonic dual-feed nozzle. Unlike conventional methods of preparing sustained release microspheres by spray-drying a single liquid containing a biodegradable polymer, a drug, an additive and a solvent through a single-feed nozzle, the present method is characterized by simultaneously spray-drying two liquids with different compositions for preparation of the sustained release microspheres respectively through internal and external channels of an ultrasonic dual-feed nozzle to coat sprayed droplets through the internal channel with other sprayed droplets through the external channel. The present method is effective in achieving a low initial release and a desired continuous release.