An increasing number of decision support systems based on domain knowledge are adopted to diagnose medical conditions such as diabetes and heart disease. It is widely pointed that the classical ontologies cannot sufficiently handle imprecise and vague knowledge for some real world applications, but fuzzy ontology can effectively resolve data and knowledge problems with uncertainty. This paper presents a novel fuzzy expert system for diabetes decision support application. A five-layer fuzzy ontology, including a fuzzy knowledge layer, fuzzy group relation layer, fuzzy group domain layer, fuzzy personal relation layer, and fuzzy personal domain layer, is developed in the fuzzy expert system to describe knowledge with uncertainty. By applying the novel fuzzy ontology to the diabetes domain, the structure of the fuzzy diabetes ontology (FDO) is defined to model the diabetes knowledge. Additionally, a semantic decision support agent (SDSA), including a knowledge construction mechanism, fuzzy ontology generating mechanism, and semantic fuzzy decision making mechanism, is also developed. The knowledge construction mechanism constructs the fuzzy concepts and relations based on the structure of the FDO. The instances of the FDO are generated by the fuzzy ontology generating mechanism. Finally, based on the FDO and the fuzzy ontology, the semantic fuzzy decision making mechanism simulates the semantic description of medical staff for diabetes-related application. Importantly, the proposed fuzzy expert system can work effectively for diabetes decision support application.