Research subject: Energy is an integral part of human life and from the beginning of history, mankind is looking for a way to control it to provide the basic needs. One of the available energy sources is fossil energy that has been considered due to the huge amount of energy. Microbial fuel cell is a bioreactor which converts the chemical energy stored in chemical bonds of the organic compounds to electrical energy through the catalytic reactions. Research approach: In this paper, two types of classical PI and MPC controller are used to investigate the voltage control of a two chamber microbial fuel cell using the model which has been presented by Esfandyari et al. [1, 2]. Considering the features of the proposed model, it can be used to optimize and control the MFC in continuous and batch modes. For this purpose, a classical PI controller based on internal model and MPC controller was designed and implemented. Based on the designed controllers, the adjustment of substrate input flow rate was implemented considering the distribution such as substrate input concentration or the uncertainty of the process model parameter such as Ks and rmax. Main results: For to control the output voltage, step change of 5 units was made in setpoint (inlet flowrate to anode chamber). The values of absolute integral error, rise time and overshoot for the classical PI controller were 3. 75, 13. 159, and 0. 091, respectively, while these values were 0. 035, 11. 908, and 0. 142, respectively for the MPC controller. Considering the achieved data, it can be concluded MPC controller performed better than the classic PI controller.