Desert oasis wetlands are distributed along the Heihe River, especially in lowland oases along the middle reach of the river, in northwestern China. Landscape maps of the wetlands in 1990, 1995, 2000, and 2006 were compiled based on data collected from Landsat TM and ETM+ images using GIS and analyzed in July 2008. Various landscape indices were calculated using the landscape structure analysis software FRAGSTATS, at both class and landscape levels. The results showed that floodplain wetland is the dominant type of wetlands in the middle reach of the Heihe River, followed by non-forested peatland, then river and reservoir wetland, with the proportion of shrub-dominated wetland low. During these 16 years, the area of wetlands in our study area decreased by 38.4%, or 107.8 km2. The major type of wetland lost in the study area was non-forested peatland during the first five years, but floodplain wetland since then. The landscape pattern shows that the fragmentation level is very high, especially in the floodplain wetlands: the patch density increased by 154% during the study period. It is clear that the wetlands along the middle reach of the Heihe River have become increasingly fragmental during the past 16 years.