Cross-linked starch microspheres were prepared using different kinds of cross-linking agents. The influence of several parameters on morphology, size, swelling ratio and drug release rate from these microspheres were evaluated. These parameters included cross-linker type, concentration and the duration of cross-linking reaction. Microspheres cross-linked with glutaraldehyde had smooth surface compared with those prepared with epichlorhydrine or formaldehyde. The particle size increased with increasing the cross-linking time and increasing the drug loading. Swelling ratio of the particles was a function of cross-linker type but not the concentration or time of cross-linking. Drug release from starch microspheres was measured in phosphate buffer and also in phosphate buffer containing alpha-amylase. Results showed that microspheres cross-linked with epichlorhydrine released all their drug content in the first 30 minutes. However, cross-linking of the starch microspheres with glutaraldehyde or formaldehyde decreased drug release rate. SEM and drug release studies showed that cross-linked starch microspheres were susceptible to the enzymatic degradation under the influence of alpha-amylase. Changing the enzyme concentration from 5000 to 10,000 IU/L, increased drug release rate but higher concentration of enzyme (20,000 IU/L) caused no more acceleration.