Abstract: The aim of the present study was to evaluate the therapeutic effect of Mongolian medicine composition compound on mastitis in mice. The mastitis model was prepared by intrathymic injection of mixed culture suspension of Escherichia coli（E.coli） and Staphylococcus aureus（S. aureus）. At 24 h after challenge,the mice in positive control group,negative control group,and Mongolian medicine composition compound group were given ciprofloxacin,normal saline,and Mongolian medicine composition compound by intragastric administration once daily for 3 consecutive days. At the 24 h after challenge（pre-treatment） and 72 h after administration（post-treatment）,the clinical symptom and histopathological change of mammary gland of the mice were observed,and the content of TNF-α and IL-6 in mammary gland tissue homogenates and the total bacterial count in mammary gland were determined. The results showed that the Mongolian medicine composition compound was able to repair the injury of the mammary gland caused by co-infection of E. coli and S. aureus and significantly reduce the content of TNF-α and IL-6 as well as total bacterial count in mammary gland of mastitis modle mice（P〈0.05）. The Mongolian medicine composition compound shows therapeutic effect on mastitis in mice caused by co-infection of E. coli and S. aureus.