Abstract: Objective To investigate the relations between different compositions of Gegenqinlian decoction and their effects on experimental shigellosis in rabbits to explore the composition protocol of Gegenqinlian decoction. Methods Rabbit models of intestinal invasion induced by Shigella flexneri was established by directly inoculating the bacterium in the colon after cecum bypass operation. The effects of different compositions of Gegenqinlian decoction on the indexes of colitis and the bacterial count of Shigella in the colon content and colon tissue were investigated by orthogonal design. Results According to the bacterial count of Shigella in the colon, Coptis chinensis franch and Scutellaria baicalensis Georgi are the main effective drugs, but they antagonized each other, so that the best combination protocol was Coptis chinensis Franch only. Conclusion Among the components of Gegenqinlian decoction, Coptis chinensis franch has the strongest pharmcological effect against bacteria and Glycyrrhina wralensis fisch is the most effective to ameliorate pathological lesions.