Abstract: In order to reduce the losses caused by calf diarrhea on large-scale farms, the incidence of calf diarrhea was investigated. Clinical diagnosis and pathogenic investigation were carried out by laboratory diagnosis method, and the therapeutic effects of different treatment methods on calf diarrhea were discussed. The results showed that the pathogens causing large-scale diarrhea in calves were not single, but mixed infections. After laboratory diagnosis, the bacterial pathogens were Escherichia coli and Salmonella. The highly sensitive drugs were sulfamethoxacil sodium, florfenicol and enrofloxacin. The mortality of diseased cattle could be effectively reduced by the corresponding treatment according to the disease situation of diseased cattle. The cure rate of oral method was only 38.74% in mild diarrhea group, while that of intravenous infusion method was the highest (58.18%) in severe diarrhea group. In the actual production process, we can adopt preliminary treatment according to the condition of cattle, in order to reduce the death rate of cattle and the expenditure of human and financial resources. When the preliminary treatment method could not cure for a period of time, it should be transferred to other more in-depth treatment methods.