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Landscape fragmentation in wetlands usually implies degradation of its ecological functions. landscape fragmentation divides wetlands into isolated islands, which disturbs the energy flow and nutrient cycling within the wetland. Research into the development and causes of landscape fragmentation in wetlands is urgently needed for effective monitoring and protection of wetlands. We use a combination of techniques including remote sensing, a landscape index model, and redundancy analysis to analyze landscape fragmentation and its driving forces in the middle reaches of the Heihe River from both temporal and spatial perspectives. A new mathematic morphological method that enhances the credibility of landscape fragmentation analysis without changing the original pixel size of the interpreted data is proposed for the calculation of landscape indices. The combination of this new mathematic morphological method and traditional landscape pattern indices enhances the evaluation strategy for landscape fragmentation. Our results demonstrate that the fragmentation processes that affect the wetland landscape of the study area are primarily represented as the shrinking of core wetland area and decrease in mean size of wetland patches. Our results also show an increase in the fragmentation index (FS) of the landscape in recent decades. The impacts of natural factors on wetland landscape fragmentation processes are typically reflected in changes in climate and hydrology. In the study area, temperature, which is more important than precipitation in driving wetland landscape fragmentation processes, cannot be omitted. In addition, our analysis proves that unnecessary human activity is a major threat for sustainable development and maintenance of wetlands. (C) 2014 Elsevier Ltd. All rights reserved.