Abstract: OBJECTIVE  Based on the zebrafish in vivo model, the compatibility of psoralen for ameliorating medicinal property was singled out to explore its detoxification mechanism and provide a theoretical basis for Clinical medication safety.METHODS   Using 1 to 6 dpf zebrafish after fertilization, the effects of different medicinal property on zebrafish was studied. the morphology/behavior of fish organs was observed and the number of deaths was counted. It determines the safe concentration by rapid screening. Psoralen is used as a representative toxic component to observe different medicinal property and their compatibility toxicity changes for zebrafish, that screen effective attenuated medicinal property and ingredients. RNA-seq was used to get the transcriptome of treating with aucubin (the representative and active ingredient of Eucommia) and psoralen to establish Gene expression profiling (DGE) library, Hepatotoxicity-related gene was selected by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. The differentially expressed genes in liver-related pathways were screened out and the detoxification mechanism of aucubin was preliminarily explored.RESULTS   It shows that aucubin can significantly reduce the liver toxicity of psoralen on zebrafish with drug compatibility. Enrichment analysis of RNA-Seq showed that compared with the psoralen group, expression of gene in the toxicity, cancer, immune activation, and chemical carcinogenic signals were significantly reduced, neurotrophic factors, Longevity regulation, platelet activation signal pathway enhanced in addition of aucubin, among which the gene names as gpx1b, pgd, rrm2, gstp2, anpepb, cyp1a, prf1.5, nfκb2 about attenuating toxicity after compatibility, which is worthy of attention.CONCLUSION   Taking advantage of the rapid evaluation of zebrafish in vivo, toxicity evaluation based on processes in vivo can be achieved. On the one hand, the compatibility of the representative component of psoralen with clear toxicity quickly targets the attenuated medicinal property and composition. On the other hand, the RNA-seq can analyze mechanisms that attenuate toxicity with compatibility of medicines. they have certain significance to its clinical medicine and theory of compatibility to detoxify.