Objective To study action mechanism of Shuanghuang Xiaocuo Pills for treatment of rabbit ear acne models. Methods Totally 48 male Japanese white rabbits were divided into blank group, model group, positive medicine group, and Shuanghuang Xiaocuo Pills low, medium, and high dose groups through random number table method. Except for blank group, other groups established rabbit ear acne models. After the models were established, these groups received gavage with relevant medicine, once a day, for 14 days. Then all the rabbit models were under blood sampling. Radioimmunoassay was used to detect contents of IL-8 and TNF-α in serum. Results Compared with blank group, the contents of IL-8 and TNF-αincreased significantly in the model group (P<0.01). Compared with model group, except for Shuanghuang Xiaocuo Pills low dose group, the contents of IL-8 and TNF-αdecreased significantly in other treatment groups (P<0.01). Conclusion Shuanghuang Xiaozuo Pills can treat acne by reducing the contents of IL-8 and TNF-αin serum.