Ventilation is a vital component of an underground mining operation, used to guarantee a safe atmosphere for workers and survive them from the hazardous and toxic gases. In the recent years, engineers have begun to apply new operation research techniques in order to optimize the ventilation systems to assist in achieving a regulatory compliance, reduce ventilation costs, and improve its efficiency. Airflow regulation optimization in mine ventilation networks is described as a minimization model whose objective function is a minimum number of regulators and energy consumption. In this work, all the previously accomplished works were first reviewed. Then a ventilation system was designed for the Western-Razmja coal mine by a manual method, and an axial fan was proposed. Subsequently, the same ventilation system was simulated using the VENTSIM 3D software. The results obtained by computer simulation showed that there was a reliable relation between the manual method and the simulation approach. In the final step, the GAMS software was used to solve a Mathematical Programming (MP) problem to minimize the overall cost of ventilation by determination of the optimum location for the fan and regulators. The final results of this work illustrated that not only the number of regulators were reduced through solving the MP model but also the total resistance of the Western-Razmja coal mine was reduced by 14% from 1.6 to 1.3. Furthermore, it was observed that the total efficiency of the proposed fan was increased.