This study was designed to investigate the effect of keratin as a natural material on the local inflammatory reaction of PLGA in vitro and in vivo. We manufactured five different ratios of PLGA/keratin hybrid materials, with each material containing 0, 10, 20, 40 and 80 wt% of keratin of PLGA by solvent casting/salt leaching method. To evaluate the influence of keratin content in PLGA materials on cell viability, NIH/3T3 mouse fibroblasts were cultured in PLGA and the 5 different ratios of PLGA/keratin scaffold. PLGA/keratin films for the in vivo study were implanted in 5-week-old Wister rats for 10 days. Cell proliferation activity was measured using WST assay. ELISA for TNF-a was conducted to evaluate the inflammatory response of cells on the PLGA/keratin scaffolds, the lowest figures showed in PLGA scaffold contained 20% keratin. We have shown that the number of vital cells was higher in the culture of the scaffold containing keratin. Analysis of histological and immunohistochemical in PLGA/keratin hybrid constructs at day 10 after implantation showed that keratin moderate immune response. This result suggest that 20% keratin of PLGA could reduce inflammatory reaction of PLGA.