Zein, as a sustained release material, was developed that permits continuous release of biologically active molecules from the microspheres, films and tablets. Ivermectin and heparin were chosen as the fat-soluble and the water-soluble model drugs, respectively. The heparin-loaded film or the ivermectin-loaded tablet were prepared based on drug-loaded zein microspheres that were obtained by the phase separation method and characterized by a scanning electron microscope and laser light scattering particle size analyzer. The biocompatibility of zein was evaluated, including human umbilical veins endothelial cells compatibility and hemocompatibility. Then the release in vitro and activity of drugs from the microspheres, films and tablets were determined. The results showed that zein and its degraded product had better biocompatibility; the sizes of microspheres could be controlled in 10nm-10μm and affected by the preparation conditions, such as concentrations of zein and drugs. Drugs in microspheres, films and tablets could be released slowly, in the mechanism of the diffusion of drugs through the matrix. Moreover, the drugs still kept the high activity.