Silk fibroin is a natural macromolecular protein derived from silkworm Bombyx mori.Its potential application as a special medical matrix has become a hot topic in medical field.However,silk fibroin synthesized by silkworm is a "heterologous" antigen for human immune system.The "heterogeneity" or immunogenicity of such biomaterial is crucial limitation to its clinical application.Whether it will trigger "nonself" recognition and stimulate immune responses in human body has become a must-be solved peoblem before the multipurpose development and the application.In this article,we review the latest researches about silk fibroin and immune competent elements incluing B cells,dendritic cells,macrophages,master cells and inflammatory cytokines.