It is an internationally acknowledged that marine protected area (MPA) is an important measure for maintaining biodiversity and rescuing endangered species. MPA can also effectively inhibit human interferences such as development and pollution discharge. The establishment of MPA is possible to fulfill the goal of sustainable management, which is to conserve marine habitat for an integrative ecosystem and a higher biodiversity. However, how to design an effective MPA remains an important research issue to be explored. In order to grasp the spatial distribution of the ecological data in the study area, the current research uses spatial interpolation tool, Kriging, provided by the Geographic information system (GIS) software. Then three spatial analytical models have been developed based on integer programming techniques. It is guarantee that all three models can find the global optimal solutions for the best protective area partitions. This quantitative approach is more efficient and effective compared to the qualitative methods in many aspects. The models are able to preserve the maximum ecological resources under the limited spatial area. Besides, the model formulation can be adjusted from different environmental impact factors to fulfill the requirements of users. The case study of the research is to design a MPA for Kaomei wetland. However the spatial analytical models developed in this research can also be applied to protected area design in land area.