At present, Natural Indigo has been used as a clinical drug for the treatment of acute promyelocytic leukemia(APL),but its effective molecular mechanism and material basis are still unclear. The purpose of this study is to construct the visible model of Natural Indigo and APL drug target protein, and to explore the molecular mechanism of Natural Indigo acting on APL. Methods:The APL microarray chip was searched through the GEO database to analyze the disease differentially expressed genes. The TCMSP database was used to screen the active ingredients of Natural Indigo. PubChem and SwissTarget Prediction were Combined to match target genes of active ingredients and enrichment analysis of target genes was done. String was used for further text mining and constructing a APL visual protein interaction network, the interaction data was read into Cytoscape, the network topology analysis was done through the plugin Centiscape. After comprehensive analysis of APL differentially expressed genes, Sybyl was constructed of drug target protein model with Natural Indigo active ingredients. Results:Three APL disease-related microarray chips, 164 differentially expressed genes, 9 Natural Indigo active components,541 component target genes were screened. These targets are more involved in apoptosis, drug combination, cancer pathway, chronic myelogenous leukemia, etc.,all of which play an important role in APL. Topological analysis showed that ELANE and CTSS were core genes, the drug target protein model prediction with the 9 active ingredients of Natural Indigo shows that indirubin and indigo have the best binding to core genes. Conclusion:APL is a complex disease regulated by multiple genes. The indirubin and indigo in Natural Indigo can act on the development of APL by combining ELANE and CTSS.