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This paper presents the design considerations and field applications on inflatable structure system to protect rapidly flooding damages in large section tunnel. This inflatable structure system is very valuably used to protect passively and rapidly the possibilities of tunnel damages by flooding threats and unusual leakage to be occurred during and after underground infrastructure. In particular, this system should be necessary in subsea tunnel. The predominant factors in the design of inflatable structure system are the leakage and friction characteristics between the inflater and tunnel liner. The analytical and experimental studies are performed to develop the design considerations and to examine the design parameters of the inflatable structure system. The analytical solutions are developed using membrane theory to suggest the design considerations. The relative friction tests of several fabric materials are also carried out to determine the friction characteristics according to the different friction conditions between inflater and tunnel surface. The test results show that the friction coefficients in wet surface condition are about 20% lower than the values in dry surface condition. In addition, virtual design of tunnel protection system for two virtual subsea tunnel sites which is under reviewing in Korea, is carried out based on this research. It is expected that the results of this research will be very useful to understand the inflater structure design and development the technology of tunnel protection structures in the future.