Through this work what is sought is to propose a method that allows to implement in a practical, accurate and effective a Simulation Model Based on Agents of Regional Innovation System (RIS), which has been developed within the project “Analysis of the structure, relations and dynamics of Agents of the Regional Innovation Systems” led by the researching groups “GISAI” and “GTI” that belongs to the “Universidad Pontificia Bolivariana” Medellin. This method proposal is focused on a review of the most important needs of Regional Innovation Systems and how these needs must be satisfied step by step through the structure of the simulation model in its application.