Regional research is a powerful approach to understanding the Earth System, which is necessary for deepening global change research. Some integrated regional cases study from Southern Africa, South Asia, East Asia, Southeast Asia, etc. and some great regional projects such as LBA, AMMA, MAIRS and ProMed indicate that the outcomes of regional change research are the great contribution to a better understanding of the Earch System as a whole, and the integrated experiment, modelling and analysis are the powerful tools for enhancing understanding of the Earth System. Some key scientific issues in regional environmental change should be focused on: (i) the response and adaptation of integrated regional key process to global change, such as land surface process, land-ocean interactions in the coastal zone and regional climate change; (ii) regional marginal phenomena, threshold and catastrophe; (iii) regional orderly adaptation of human activity to global change. It is necessary for regional studies to make regional programs related to global change, Earth observation at the regional scale, new integrated method, regional experiment and scaling, Earth modeling and simulation, etc.