Abstract: With glutaraldehyde as cross-linking agent, LAMV-SALG/CS microspheres were prepared by means of the inverse emulsion dispersion and ionic bonding. The amino of lamivudine and carboxyl of sodium alginate can form weak salt bonds, so the drug can be stably wrapped in the inner layer of the microspheres, and then chitosan was crosslinked by glutaraldehyde to form the shell layer of the composite microspheres. The physicochemical properties and the drug-release performances of the microspheres were investigated. The microspheres have a regular spherical shape and an average diameter of about 2 m. The drug mass content was 116%, and the drug encapsulation efficiency reached to 703%. The amino groups in chitosan combined with the carbonyl group in glutaraldehyde to form the cross-linked network, and lamivudine have been enwrapped inside the microspheres. The drug-release measurement results indicated that the microspheres have a satisfactory performance of releasing lamivudine at slow and steady rate. The drug release period corresponding to cumulative drug-release rate of 27% reached to 82 h in the acid medium. With the increase of the concentration of SALG, the releasing rate of lamivudine decreased. The releasing rate of lamivudine in acidic buffer was faster than in alkaline one. Drug-releasing rate of the microspheres prepared in the alkaline reaction medium was faster than that prepared in weak alkaline and acid ones.