Nature reserves play an important role in maintaining biodiversity and improving ecological environment quality. It is not clear how the ecological environment quality in nature reserves changes and its response to the natural factors and human activities. Understanding these rules is of great significance to the construction of ecological civilization and the biodiversity protectionin China. Based on China's high-resolution eco-environmental quality (CHEQ) dataset and natural factors from 2001 to 2019, the changing patterns of the ecological environment quality of the nature reserves in China were investigated and the corresponding contributions of the main driving forces, natural factors and human activities to these changes were distinguished using the methods of trend analysis and multiple regression residuals analysis. The results showed as follows:① CHEQ index of nature reserves in China indicated multi-stage fluctuation change and an overall slightly decreasing trend, with an average trend rate of -0.54×10^-3/a. Overall pattern of CHEQ was high in the south and east region and low in the north and west region. ② The combination of natural factors and human activities was mainly distributed in the experimental zone and buffer zone of the nature reserves and was the main factor of environmental degeneration. The impacts of natural factors on CHEQ change ranged from -3×10^-3/a to 0/a, while the impacts of human activities changed from -1×10^-3/a to 2×10^-3/a. ③ The contribution rate of natural factors to CHEQ change in China's nature reserves was more than 75%, and the contribution rate of human activities to CHEQ change was less than 45%. Among the natural factors in this study, precipitation had the greatest impact on the ecological environment quality of China's nature reserves, while surface runoff factor had the least impact. While making up for the shortcomings of the existing studies, this work is expected to provide the quantified support on the coordination between ecological conservation and economic development in the future, and provide scientific knowledge for formulating the corresponding policies.