To Observe the skin irritation of dried extract powder and different extraction parts of Zushima，and predict its irritant components and mechanism of action based on bioinformatics.Methods:SD rats were randomly divided into integral skin group and broken skin group.The skin condition was observed 7 days after drug administration and 3 days after drug withdrawal.The TCMSP were used to query the irritant components and targets of Zushima.Disease targets were collected through GeneCards，OMIM and other databases.Metascape platform was used for GO enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis.The core targets and the stimulating components of Zushima were used for molecular docking.Results:The low-dose group and medium-dose group of Dried Zushima extract powder had slight erythema and edema on broken skin.The high-dose group of Dried Zushima extract powder，petroleum ether parts and dichloromethane parts had slight erythema and edema reaction on integral skin and broken skin.There was no erythema and edema reaction on integral skin and broken skin in ethyl acetate and water layer parts.Seven irritant components were screened from the active ingredients of Zushima，which were mainly enriched in PI3K-AKT，Ras，MAPK，Rap1 and Relaxin signaling pathways，and so on.Molecular docking results showed that the key targets formed stable structures with active components Daphnetoxin，Luteolin and Physcion.Conclusion:The high-dose of Dried Zushima extract powder has slight skin irritation，which may be due to the complex effects of the Daphnetoxin，luteolin and Physcion in petroleum ether and dichloromethane to promote the generation of inflammatory factors through multi-target and multi-pathway，causing slight erythema and edema of the skin.