The goal of this study was to investigate release tendency of brain-derived neurotrophic factor (BDNF) from poly(L-lactide-co-glycolide) (PLGA) and small intestine submucosa (SIS) scaffold prepared by ice-leaching method. A porous scaffold consisting of PLGA and SIS as carrier of BDNF has been prepared in the presence of ice particle. SEM image of the PLGA/SIS scaffold showed an interconnected pore structure. The release behavior of BDNF loaded PLGA/SIS scaffold was examined for 4 weeks period at phosphate buffered saline (PBS, pH 7.4) at 37 oC. The sustained release of BDNF over 4 weeks was observed from the PLGA/SIS scaffold. These results indicate that the sustained release of BDNF from PLGA/SIS scaffold can be very useful for application in the tissue engineering.