Analyzing the dynamic changes of lakes in Tibet, the world’s climate sensitive region, in the background of global warming and economic development, is of great significance to revealing the environment evolution features. According to the lake boundary information obtained by Landsat remote sensing images from 1990 to 2015, we analyzed the dynamic changes of spatial and temporal distribution of lakes in Tibet in the past 25 years. We also investigated into the main driving factors of lake change in terms of climate factor and human factor, and further analyzed the lake change in response to climate change. Results show that in the past 25 years, the number of lakes in Tibet has increased by 261 and the area of lakes has increased from 24 161.1 km² to 30 549.2 km². In temporal scale, lake area experienced a severe shrinkage in 1990-1995, and then expanded rapidly in 1996-2006; in 2007-2013, the expansion alleviated. The temporal transformation can be well reflected by precipitation, temperature, and evapotranspiration. In spatial scale, the variation of lake area differs apparently: in the middle of Tibet, low temperature and evapotranspiration as well as high precipitation gave rise to the rapid expansion of lake area; whereas in north Tibet, despite high temperature, low precipitation and large amount of evapotranspiration, the melting of glaciers and frozen soil caused by high temperature could be a possible factor of lake expansion; in the Himalayas, evapotranspiration far exceeding precipitation led to lake shrinkage. In addition, although human activities contributed to the local demand for lakes and other water resources, the area of lake has expanded, indicating that climate is a main driving factor of lake change in Tibet.