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This study is to forecast the damage of smallpox as a biological weapon and to measure the effect of potential responses (quarantine, vaccination and cure) to the spread of smallpox infection when a smallpox bioterrorism attack occurs. We designed the smallpox spreading simulation model through the literature study on a basis of some existing infectious disease models such as SIR, SEIR model by using Vensim program. In order to evaluate the performance of responses to smallpox, we measure the total infection population, infection sustaining duration, average infection rate and the infection spreading behavior of the smallpox.This study can help those who are related to the bioterrorism forecast the present and possible demage, and take more effective actions for minimizing the damage by smallpox bioterrorism.