Sarcocystosis is an emerging disease in yaks, and Sarcocystis infection creates a health threat to humans and animals. During a recent study, Sarcocystis infection was detected in yaks by means of morphological observation using hematoxylin and eosin, Giemsa, and acridine orange staining. The species of Sarcocystis isolated from yaks were analyzed and identified phylogenetically. To establish the best model for culturing sarcocystosis isolated from yaks in vitro, four different cell lines—PAMs, Pk15, HeLa, and Vero cells—were used. The effects of sarcocystosis isolated from yaks on the MAPK signaling pathway in Vero cells were detected using Wes automatic Western blot and RT-qPCR. The results from the phylogenetic tree indicate that the sequences of Sarcocystis obtained from yaks in this study were grouped within the Sarcocystis cruzi clade. Results also have shown that S. cruzi had a higher proliferation rate in Vero cells, suggesting that Vero cells are more suitable for the long-term culturing of S. cruzi in vitro. Results also indicate that S. cruzi infecting Vero cells could cause the activation of ERK1/2 pathway, while inhibiting the ERK1/2 pathway could suppress S. cruzi infection in Vero cells. Therefore, the study and exploration of Sarcocystis-host relationships can effectively provide certain theoretical knowledge and the basis for the treatment of clinical diseases and the development of Sarcocystis drugs.