Effect of additional chemicals at different culture conditions was studied in detail on newly isolated Rhizopus oryza (RO, IIT KGP) to maximize protease synthesis. The surfactants and metal ions when added to the basal medium individually were acted as inducers. The combined effect of these inducers on protease production was also studied in detail and a semiempirical mathematical model based on the data obtained was proposed to optimize their effects. A 2.5 fold increase in the protease production was possible by optimizing the two variable inducers system.