Streptomyces sp. 2M21 was evaluated for keratinase production in bioreactors using chicken feathers. Firstly, optimization of bioengineering parameters (agitation and aeration rates) using Response Surface Methodology was carried out in 2 L bioreactors. Optimized conditions identified by the modified quadratic model were verified as 150 rpm and 1 vvm experimentally corresponding to 351 U/ml of keratinase activity. Moreover, scaling up sequentially to 20 L bioreactors was implemented using constant impeller tip speed and constant mass transfer coefficient as key scale-up parameters. The keratinase activity in 5, 10 and 20 L bioreactors showed similar results with the one of shake flasks (412 U/ml) and 2 L bioreactors (351 U/ml)with respect to the keratinase activity values of 336, 385 and 344 U/ml, respectively. The results suggest keratinase production by evaluating chicken feathers in commercial level. Furthermore, this study has potential to contribute industrial scale production of keratinase by Streptomyces sp. 2M21 using the proposed bioreactor conditions.