--- - |2- The protein‐protein interaction network of insecticide resistance molecular mechanism (a). Sub network of nodes with higher value (b). The degree centralityin (c) of insecticide resistance network in D. melanogaster. The color of every node is changed according to the different degree values or combined score. Prosalpha6, CG9674, RpL40, Akap200, Prosalpha6 are the highest value in DC, BC, CC, CU, EC respectively. They are diamond shaped. The number in or outside parentheses is the degree centrality or protein ID code. Abstract The problem of resistance has not been solved fundamentally at present, because the development speed of new insecticides can not keep pace with the development speed of resistance, and the lack of understanding of molecular mechanism of resistance. Here we collected seed genes and their interacting proteins involved in insecticide resistance molecular mechanism in Drosophila melanogaster by literature mining and the String database. We identified a total of 528 proteins and 13514 protein–protein interactions. The protein interaction network was constructed by String and Pajek, and we analyzed the topological properties, such as degree centrality and eigenvector centrality. Proteasome complexes and drug metabolism—cytochrome P450 were an enrichment by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. This is the first time to explore the insecticide resistance molecular mechanism of D. melanogaster by the methods and tools of network biology, it can provide the bioinformatic foundation for further understanding the mechanisms of insecticide resistance. - 'Archives of Insect Biochemistry and Physiology, EarlyView. '