[Background] Streptococcus suis type 2 is an important pathogen that harms the pig industry and causes significant losses to the pig industry in China. So far, there is still a lack of model of encephalitis caused by Streptococcus suis type 2 infection, so we establish appropriate models for clinical drug development and mechanism research to lay the foundation for prevention and control of the disease. [Objective] Construction of Streptococcus suis type 2 infection in piglets induced encephalitis model, the clinical changes observed in piglets infected, pathological changes, Isolation and PCR analysis confirmed successful model building. [Methods] Six healthy ternary crossbred piglets were randomly divided into two groups, A and B. Group A piglets were inoculated with Streptococcus suis, and group B was inoculated with normal saline as the control. The clinical symptoms, necropsy changes and histopathological changes of group A piglets were observed. [Results] Group A piglets had elevated body temperature, depression, lethargy, and severe neurological symptoms, or even death. Severe lesions occur in the organs, such as swelling, necrosis, and dissolution of neurons in the spinal cord and brain. Focal necrosis and post-necrotic space are seen in the purkinje cell layer and granular layer of the cerebellar gray matter. [Conclusion] A model of encephalitis in piglets infected with S. suis type 2 was successfully constructed.