The water eco-health has become an important goal of regional environment management and a new trend of eco-environmental fields in China and abroad. In the areas around Chaohu Lake of China, the rapid industrialization and urbanization have led to ecological health problems, such as water quality deterioration, vegetation degradation and ecosystem degeneration. This paper aims to give some advices on achieving the healthy development of water ecosystem based on spatial development and regulation zoning in the areas around Chaohu Lake. After building the evaluation index system composed of water ecological sensitivity and water ecological pressure, this paper discusses the methods of spatial zoning which is related to both regional development and ecological environment protection, based on 500 m×500 m grid units and ArcGIS software, as well as the comprehensive evaluation of single factor and multifactor analysis. The areas around Chaohu Lake, serving as a case study, are divided into four types by the method of two-dimensional quadrant analysis, namely, high-sensitivity and high-pressure area, high-sensitivity and low-pressure area, low-sensitivity and high-pressure area, and low-sensitivity and low-pressure area, representing 2.66%, 20.46%, 13.01 and 63.87% of the total area respectively. Different measures are put forward according to different types of areas. Firstly, the areas around Chaohu Lake generally should adopt a policy on low density development prioritizing the ecological and cultural protection. As an important drinking water source and ecological barrier areas in Chaohu and Hefei city, the areas around Chaohu Lake is expected to give a strict protection of the natural reserve, existing mountain, water and wetland landscape, forest parks, scenic areas, lake shelterbelts and so on. Secondly, learning from previous lessons on the development models of lakeside districts in other regions and countries, the development model in the areas around Chaohu Lake should adopt appropriate measures suiting local conditions:the belts along the main rivers into Chaohu Lake have the higher sensitivity to water environment, are not suitable for large-scale development and construction, and need to strengthen the ecological restoration and environmental protection. Thirdly, the northern Binhu new district of Hefei city, Chaohu city and their towns have higher pressures on water ecosystem from high-density development activities, is in urgent needs of the model transformation and structure upgrade in industrial and urban development, and implements strict access standards to environmental and pollution emissions. Lastly, although some regions with lower ecological sensitivity and pressure can adopt different measures and development models relying on local resources and their own advantages, a strict control of new emissions of pollutants and maintenance of healthy development of ecological water are of prime importance.