Abstract: Abstract: Water use efficiency (WUE) of vegetation is an important parameter coupling the carbon cycle with water flux in the terrestrial ecosystem, as far as to the whole earth. Under the background of climate change, WUE is likely sensitive to the climatic factors. But for cropland, cultivation, as well as the climate change, also exerts great influences on the long-term WUE. However, questions are still remained about the spatio-temporal distribution of WUE and its affecting factors, for example what factors significantly affect the cropland WUE inter-annual variations and whether the effects of these factors vary with different regions at regional scale. Therefore, in order to obtain the change characteristics of WUE and the influential factors, this study focused on the application of data from moderate-resolution imaging spectroradiometer (MODIS), estimated the cropland WUE, analyzed the spatio-temporal patterns and evaluated the effects of climate change and two kinds of cultivation, irrigation and fertilization in the cropland in the middle of east of China. The cropland multiyear averaged WUE and its dynamics were evaluated in five regions that were delineated according to the dynamics of crop planting structure including: RegionⅠrepresenting the area where the crop was dominated by wheat and corn with rapidly expanding maize planting area, Region Ⅱwhere the crop was dominated by wheat and corn with expanding planting area, Region Ⅲ where the crop was dominated by wheat and rice with expanding planting, Region Ⅳ where the crop was dominated by rice with expanding rice planting area and Region Ⅴdominated by rice with shrinking rice planting area. Results showed that multiyear averaged WUE was the largest in the North China Plain, Shandong Peninsula and the coast region in Jiangsu, with an average value of 2.0 g/kg, while in the Northeast China Plain and Hilly Region of Southeastern, the multiyear averaged WUE was approximately below 1.5 g/kg. Generally, multiyear averaged WUE was higher in the northern dryland field rather than in the southern paddy field. During the period from 2003 to 2012, the cropland WUE had an increasing trend in the middle and east of China. Compared to the southern paddy field, the northern dryland field had a larger rise. The largest increasing trend was found in the North China Plain where the cropland WUE increased by 0.02 g/kg per year. The cropland WUE showed a decreasing trend in the Hilly Regions of Southeast, area between Yangtze River and Huaihe River and Sanjiang plain with the largest decreasing amplitude approximately -0.007 g/kg per year. Generally, the increasing trend was more prevalent in the northern dryland field rather than in the southern paddy field. Correlation analysis showed that precipitation, effective irrigated area and fertilization were significantly (P＜0.05) correlated with WUE inter-annual variation in Region Ⅱ, solar radiation and precipitation in Region Ⅲ and annual average temperature in Region Ⅳ. For Region Ⅱ, due to the high co-linearity between precipitation with effective irrigated area and fertilization, the effects of irrigation and fertilization seem to be negligible for the inter-annual variation of cropland WUE. In the northern dryland field, precipitation was the main factor, while precipitation and annual average temperature were the main factors in the southern paddy field. In the northern dryland field, precipitation significantly controlled cropland evapotranspiration, while in the southern paddy field, the gross primary productivity was strongly regulated by annual average temperature. It is indicated that the different effects of climate on cropland WUE in the middle and east part of China, which will be of great importance on the rational utilization of water resource and the sustainable development of ecological environment in cropland.