Footrot is a highly contagious disease of the feet of animals, characterized by the separation of keratinous hoof from the underlying tissue. Co-infection of Dichelobacter nodosus and Fusobacterium necrophorum is the main reason of footrot in clinical. Environmental factors, such as warm and wet weather and pasture quality, etc. all are conducive for indirect transmission of bacteria among individuals. Fusobacterium necrophorum, which product several virulence factors such as leukotoxin, hemolysin, hemagglutinin, play an essential role in the infection process. Moreover, a lot of potential differential expression (PDE) proteins were found in plasma samples from dairy cattle with footrotsome of which may be valuable for use as diagnostic biomarkers, the possible mechanism which these proteins involved in the pathogenesis of footrot were analyzed in this paper.