Objective To observe the effect of sanfukechuangao acupoint application on changes of interleukin-18 (IL-18), eosinophils (EOS) and pulmonary pathology in asthma model of guinea pigs, and its underlying mechanism thereof. Methods A total of 60 guinea pigs were randomized into normal control group, asthma model group, acupoint-application 1 h group, acupoint-application 3 h group, acupoint-application 6 h group and dexamethasone group. Asthma model was established by intraperitoneal injection of 10%ovalbumin (OVA,1 mL) and forced inhalation of atomized 2%OVA. Skin preparation and external application of Chinese medicinal herbs were made on back of guinea pigs, and Feishu,Xinshu,Geshuwere selected in acupuncture points). Levels of IL-18 and EOS were detected by immunohistochemisty method. Results Compared with model group,the levels of IL-18 and EOS were significantly decreased, the pathological changes were significantly reduced in three acupoint-application groups. The effectiveness of acupoint-application 3 h group was the best in three groups. Conclusion Sanfukechuangao acupoint application can influence the levels of IL-18 and EOS effectively, and relieve phlegmonosis injuries in pulmonary tissue of asthma model of guinea pig.