In this study, different context-dependent effects of imidacloprid exposure on the honey bee response were studied. Honey bees were exposed to different concentrations of imidacloprid during a time period of 40 days. Next to these variables, a laboratory-field comparison was conducted. The influence of the chronic exposure on gene expression levels was determined using an in-house developed microarray targeting different immunity-related and detoxification genes to determine stress-related gene expression changes. Increased levels of the detoxification genes encoding, CYP9Q3 and CYT P450, were detected in imidacloprid-exposed honey bees. The different context-dependent effects of imidacloprid exposure on honey bees were confirmed physiologically by decreased hypopharyngeal gland sizes. Honey bees exposed to imidacloprid in laboratory cages showed a general immunosuppression and no detoxification mechanisms were triggered significantly, while honey bees in-field showed a resilient response with an immune stimulation at later time points. However, the treated colonies had a brood and population decline tendency after the first brood cycle in the field. In conclusion, this study highlighted the different context-dependent effects of imidacloprid exposure on the honey bee response. These findings warn for possible pitfalls concerning the generalization of results based on specific experiments with short exposure times. The increased levels of CYT P450 and CYP9Q3 combined with an immune response reaction can be used as markers for bees which are exposed to pesticides in the field.