Fermentative production of nattokinase, a potent fibrinolytic enzyme using Bacillus natto NRRL 3666 was optimized by statistical optimization methods at shake flask. In addition, the production scheme based on optimum medium was scaled-up in 5-L lab-scale fermenter containing 2.5 L working volume. Further, unstructured mathematical models were proposed for kinetics of batch fermentation at shake flask as well as fermenter level for nattokinase. Enhanced production of nattokinase from $188{pm}2.4$ to $1,190.68{pm}11$ U/mL within 40 hr was achieved at shake flask. Nattokinase production improved to 1,932 U/mL in fermenter, which was 1.6 fold higher than shake flask. The production process was significantly reduced to 26 hr in the fermenter. The proposed models showed better prediction for experimental data with respect to biomass formation ($R^2$ > 0.96), enzyme production ($R^2$ > 0.99), and substrate utilization ($R^2$ > 0.96). The present work showed successful optimization of medium for hyperproduction of nattokinase.