In order to accelerate health care information process, to improve patient safety and quality and benefits of healthcare, and to provide comprehensive electronic patient record, we propose an intelligent middleware with two-layer knowledge-based architecture, which can integrate heterogeneous health care applications dynamically. In the first data sources integration layer, standard-based health care ontology and global API metadata are achieved, which make authorized health care applications "understand" and operate heterogeneous data sources automatically and transparently. Based on this unified information, in the second application integration layer, configurable standard-based application workflow integration facilitates the communication and interoperation between the disparate health care applications. The proposed knowledge-based architecture can optimize standard-based medical data exchange, and improves the flexibility, interoperability, maintainability, scalability and extensibility of health care information systems.