In this paper auto-tuning scheme of PID controller based on the reference model has been studied for a Process control system by immune algorithm. Up to this time, many sophisticated tuning algorithms have been tried in order to improve the PID controller performance under such difficult conditions. Also, a number of approaches have been proposed to implement mixed control structures that combine a PID controller with fuzzy logic. However, in the actual plant, they are manually tuned through a trial and error procedure, and the derivative action is switched off. Therefore, it is difficult to tune. Since the immune system possesses a self organizing and distributed memory, it is thus adaptive to its external environment and allows a PDP (Parallel Distributed Processing) network to complete patterns against the environmental situation. Simulation results reveal that reference model basd tuning by immune network suggested in this paper is an effective approach to search for optimal or near optimal process control.