This paper takes Chang-Zhu-Tan Urban Agglomeration as study area. Based on the vegetation index and land use data interpreted from Landsat TM images and combined with the population, economic and climate data, a framework model was established. The results show that: (1) the mean values of wetland ecological security index in 2000, 2005 and 2010 for Chang-Zhu-Tan Urban Agglomeration were 0.7268, 0.7151 and 0.7196, respectively. The status of regional wetland ecological security was good, and the ecological security degree was relatively safe. In the recent decade, the overall performance of the regional ecological security index had decreased, and the decrease of the corresponding area was 21577 km2, which accounted for 22.28% of the total land area; (2) in this study area, there is obvious difference of regional ecological security, that the first-class wetland ecological safety area mainly distributed in the surrounding regions of Dongting Lake, the second-class ecological safety region distributed along the major rivers, the third-class ecological safety area mainly distributed in the border area of two or three cities, and the fourth-class wetland ecological safety area mainly distributed in Yueyang city, Xiangtan city, Changsha city and Hengyang city. (3) During the study period, the area of wetland in Chang-Zhu-Tan Urban Agglomeration has changed obviously, that the total area of wetland has decreased year after year. The fractal dimension of forest swamp, herbaceous swamp, lake, river and paddy field showed an increasing trend. The fragmentation index of ponds/rivers was significantly higher than that of other types of landscape, and the value of wetland ecosystem services was decreasing in general. Finally, the main factors affecting the ecological security of wetland were analyzed from the aspects of land use change and transition, and wetland landscape structure and function.