Sericin, one of the two main proteins of silk cocoon besides fibroin, has been wildly used as ingredient in cosmetic products and nutrition supplements; however there are considerable controversial reports on its toxicity to cells and its advantages. This work aimed to investigate cell biocompatibility of sericin both in the systems of blended silk fibroin/sericin and pure sericin films using L929 mouse fibroblasts. The effect of concentration of commercial heat extracted sericin on cell viability was first investigated in the system of silk fibroin/sericin (F/S) films using 2 types of silk fibroin, Bombyx mori Nangnoi Srisaket 1 and Bombyx mori Jul 1/1. For both types of silk fibroin, it was found the lower cell number attached and proliferated on the blended F/S films at all sericin concentrations, compared to that on glass and pure fibroin. However, proliferation rate of cells cultured on the blended F/S films was similar to that of cells cultured on glass and pure fibroin films, as confirmed by population doubling time (PDT). Cytotoxicity of sericin extracted from 4 different methods including heat, acid, alkali and urea treatments was further studied in this work in the system of pure sericin films. It could be seen that acid and urea extracted sericin films showed high percentage of cell attachment at 92% and 88%, respectively. However, number of cells proliferated on all sericin films after 48 h culture was not significantly different. This indicated that L929 cells had different proliferation rate when cultured on different types of sericin films. Among 4 extraction methods, the PDT of cells proliferated on urea extracted sericin film was lowest (27 h) and also lower than that of the blended F/S films. This study suggested that sericin extracted by urea treatment could enhance proliferation rate of L929 mouse fibroblasts.