In Korea, the Asian honey bee (Apis cerana) and the European honey bee (Apis mellifera) (Hymenoptera: Apidae) are the two most common honey bee species. These two closely related species are known to have different sensitivity levels to various insecticides due to millennia of exposure to different pests and pesticides. It is reported that A. cerana is known to be more sensitive to several insecticides, such as amitraz, fenitrothion, and fipronil, than A. melllifera. Multiple studies investigated toxicological responses and related CYPome in A. mellifera, but little is known in A. cerana. The goal of this study is to elucidate the underlying mechanism of different toxicological responses between two bee species, with an emphasis on cytochrome P450 (P450), a significant enzyme involved in metabolic activities. The differences in basal P450 expression patterns were investigated by comparing the relative expression levels of P450 orthologs in several dissected organisms of each species. To compare the sensitivity against major insecticides, lethal doses of major insecticides relevant to both honey bee species were assessed by topical and oral ingestion bioassays. The determined sublethal doses of insecticides were applied to honey bees, and the inducibility of P450s was investigated by comparing the expression patterns of multiple P450s. From these results, this study eventually attempts to compare the toxicological differences between two Apis species with differences in induced cytochrome P450 expression levels.