When treating the 3rd instar larvae of the diamondback moth (DBM), Plutella xylostella, with sublethal doses (LC10) of chlorantraniliprole, indoxacarb and spinosad via leaf dipping, their tolerance to insecticides was significantly enhanced. By analyzing the differentially expressed genes (DEGs), we found a number of genes that respond commonly or specifically to the test insecticides. With the criteria of p value < 0.05 and Log2FC > 1/ < -1, a total of 476, 367 and 410 genes were determined to respond specifically to chlorantraniliprole, indoxacarb and spinosad, respectively. Gene Ontology (GO) analysis revealed that the cuticle reorganization is commonly associated in all treatments and the oxidative stress-related process is also shown in all insecticides except spinosad. Finally, the DEGs seemingly related with enhanced tolerance were chosen for further characterization, and reliability of the transcriptome data were confirmed by quantitative PCR. The functional categories of these DEGs included mostly detoxification related genes, cuticle proteins, energy metabolism and transcriptional regulation. While the commonly responding DEGs suggest that they are likely involved in defense against common intoxication process, the DEGs specifically responded to each insecticide suggests the presence of unique tolerance mechanisms to each insecticide depending on their different structure and mode of action. Their possible roles in the tolerance/resistance development were discussed.