Biomaterials used for tissue engineering should have the property of good histocompatibility, superb plasticity and desired degradability, so that it can be extensively applied for defect tissue repairing with excellent clinical outcome. In the past decade, silk fibroin has become one of the most favored biomaterials for its wide availability, superb performance and readiness to be shaped for different purposes in tissue engineering[1-14],. Porous scaffolds made by silk fibroin can be made into different pore size and porosity to serve for different needs of tissue repairing. The porous structure may contribute to the mass exchange in the scaffolds. However, the implanted protein scaffolds will degrade and can hardly be separated from host tissues. Therefore, little has been reported on histocompatibility experiment in vivo for silk fibroin[15-22]. In this chapter, progress in study of silk fibroin scaffold in tissue engineering application and biocompatibility research will be introduced, then our histocompatibility experiment of porous scaffolds will be reported. In our experiment, porous scaffolds were made platy and buried in subcutaneous part of the back of SD rat. Tissue reaction was observed, and the value of silk fibroin as tissue engineering scaffold material was discussed.