Although silk sericin (SS) enhances the growth and attachment of fibroblast cells, its toxicity remains questionable. We investigated the effect of SS extracted by heat with variable amino-acid content on in vitro collagen promotion and nitric oxide synthesis. After 24 h of incubation, SS, especially from the Chul 1/1 strain which has the most methionine and cysteine content, enhanced fibroblast growth. The molecular mass of heat-extracted SS from these three strains showed a slightly different range, but within 20-200 kDa, which were all identified as sericin. SS from all strains promoted type-I collagen production in a concentration-dependent manner, while SS from Chul 1/1 strain could induce the highest amount of collagen synthesis when compared to SS from other strains. Nitric oxide was found in the culture medium after activation by SS from the Chul 1/1 strain but reached a level that was not toxic to the cells. We conclude that SS is not toxic to fibroblast cells. Moreover, methionine and cysteine content in SS are important factors to promote cell growth and collagen synthesis.