To research the inference model of seeking the cause of disease from syndrome differentiation from the perspective of cognitive science. Methods: Firstly, reviewed analogic reasoning, abduction and inference by best explanation in the context of cognitive science, reviewed the thinking transformation in the process of syndrome differentiation, which is the core theory of TCM. Secondly, analyzed the logical structure of the cognitive process of seeking the cause of disease from syndrome differentiation, then made comparisons between the Qu Lei Bi Xiang and analogy or metaphor, between Si Wai Chuai Nei and abduction, between seeking the cause of diseases from syndrome differentiation and inference by best explanation. Results: There are similarities or compatibilities between the cognitive structure of seeking the cause of diseases from syndrome differentiation and analogic/ metaphorical reasoning, abduction and inference by best explanation. Conclusion:The process of seeking the cause of diseases from syndrome differentiation contains analogic or metaphorical reasoning, abduction from methodology of TCMs understanding of diseases, as well as best explanation, which reveal the inference structure of syndrome differentiation.