The drug-loaded microcapsules were prepared by alternate deposition of protamine sulfate salt (PRM) and sodium alginate (ALG) onto the surface of hydrophobic indomethacin (IDM) microcrystals through layer-by-layer (LbL) self-assembly. The morphology of drug-loaded microcapsules was characterized by SEM, and the effects of assembling layer numbers, temperature, ionic strength and pH value of release medium solutions on the IDM release property were investigated by ultraviolet spectrophotometer (UV). The results show that (ALG/PRM)n@IDM microcapsules obtained by layer-by-layer (LbL) self-assembly have a prominent impact on the IDM controlled release. The drug release rate decreases as the number layers of self-assembling and the salt concentration of release medium solutions increase, and as the pH value and temperature of releasing medium drop.