Abstract: Based on the 1975-2010 multi-temporal remotely sensed TM and ETM images and meteorological data, in combining with wavelet analysis, trend surface simulation, and interpolation method, this paper analyzed the meteorological elements’ spatial distribution and change characteristics in the middle reaches of Heihe River, and elucidated the process of wetland landscape fragmentation in the study area by using the landscape indices patch density (PD), mean patch size (MPS), and patch shape fragment index (FS). The relationships between the wetland landscape fragmentation and climate change were also approached through correlation analysis and multiple stepwise regression analysis. In 1975-2010, the overall distribution patterns of precipitation and temperature in the study area were low precipitation in high temperature regions and high precipitation in low temperature regions, and the main characteristics of climate change were the conversion from dry to wet and from cold to warm. In the whole study period, the wetland landscape fragmentation was mainly manifested in the decrease of MPS, with a decrement of 48.95 hm², and the increase of PD, with an increment of 0.006 ind·hm^-2.