Pathogenesis is the core of syndrome differentiation in traditional Chinese medicine（TCM）

reflecting the essence of struggle between healthy qi and pathogenic qi in the disease occurrence and development. From the perspective of informatics

the pathogenesis can be embodied as a complex network composed of the basic pathology corresponding to the healthy qi of the human body and/or the basic etiology corresponding to the pathogenic qi. Guided by system science

a mathematical definition of pathogenesis is established based on graph theory

namely pathogenesis network

where the basic pathology or basic etiology represents the nodes of the network（also called pathogenesis element）

and the relationship between the basic pathology or basic etiology represents the edge of the network（also called pathogenesis chain）. The holistic definition of the pathogenesis network is proposed

which transform the concept of holism of TCM syndrome differentiation into the mathematical nature of holistics（essence）; based on the definition of the pathogenesis network and the holistic definition of the network

preliminary exploration and construction of an intelligent reasoning method for differentiating the pathogenesis was explored and preliminarily constructed

namely the network differentiation. A consistency evaluation strategy was proposed for evaluating the performance of the network differentiation

and the simulation application of network differentiation was carried out in real clinical cases. The simulation results shows that differentiation based on network fully reflect the reasoning thinking of TCM practitioners.