In this paper, alternative natural refrigerant R290(Propane), R600(Butane), R717(Ammonia), R1270(Propylene) for freon refrigerant R22 were used working fluids for 2-stage compression and 1-stage expansion refrigeration system. The operating parameters considered in this study included evaporation temperature, condensation temperature, subcooling degree, superheating degree, mass flow rate ratio of inter-cooler. The main results were summarized as follows : The COP of 2-stage compression and 1-stage expansion refrigeration system increases with the increasing subcooling degree and mass flow rate ration of inter-cooler, but decreases with the increasing evaporating temperature, condensing temperature and superheating degree. Therefore, subcooling degree, mass flow rate ratio of inter-cooler of 2-stage compression and 1-stage expansion refrigeration system using natural refrigerants have an effect on COP of this system. The COP of natural refrigerants was higher than the COP of freon R22 in this study, so points to be considered are the security, the attached facilities for natural refrigerants than COP.