Next-generation grid systems where the emphasis shifts to distributed global collaboration, a service-oriented approach, and information layer issues exhibit a strong sense of automation. Requirements for these systems resemble the self-organizing and the self-healing properties of natural ecosystems. Inspired by this resemblance, we introduce some key ecological concepts and mechanisms into the design for the third-generation grid systems. In this article, a novel Ecological Network-based Grid Middleware (ENGM), which is based on Ecological Network Computing Environment (ENCE), is proposed. First, we discuss how to design the ENCE by agent-oriented approaches based on the key concepts and principles of ecosystems. ENCE provides a new computing and problem-solving paradigm by combining natural ecosystem mechanisms with agent technologies. Then, we design the ENGM with built-in mechanisms to support desirable requirements of new grid systems, namely scalability, adaptability, self-organization, simplicity, and survivability. Based on Jeffery's conceptual model, we also present a corresponding grid-computing prototype that embeds ENGM layers from the implementation point of view. The ENGM will be useful to address the challenges of the third-generation grid systems. Finally, as a demonstration, we built an ENGM platform-based commercial grid service environment and developed a prototype of enterprise supply chain management system. The experimental results demonstrate that the proposed ENGM satisfies the requirements of the next-generation grid and is suitable for new generation grid applications.