Abstract: Land use transition is one of the main drivers of regional ecosystem change in arid area, which directly affects human well-being. Based on the satellite images of 1987, 2001 and 2016, the change detection assessment model and ecological response model were used to analyze the process of land use transition and response of ecological quality during 1987-2016 in the ecologically fragile middle reaches of the Heihe River. The results showed that the land use change was significant during 1987-2016 and the total change increased significantly, as well as the continuous increase of the cultivated land and construction land. There was a strong tendency of transform from grassland to cultivated land, while the tendency of transforming unused land to other land classes was not strong under a random process of gain or loss. During 1987-2016, the ecological quality of the study area displayed a decreasing trend as a whole and the ecological land decreased by 2.8%. The land use transition with the greatest impact on the ecological environment degradation was the transition of the grassland to the cultivated land and unused land. Therefore, in order to promote the sustainable use of regional land resources and to improve the regional ecological quality, it is necessary to allocate the proportion of production land and ecological land according to the regional water resources.