Brassinosteroids (BRs) are known to protect crops from the toxicity of herbicides, fungicides and insecticides. It is shown here that application of 24-epibrassinolide (EBR) accelerated metabolism of various pesticides and consequently reduced their residual levels in cucumber ( Cucumis sativus L). Chlorpyrifos, a widely used insecticide, caused significant reductions of net photosynthetic rate (Pn) and quantum yield of PSII (Phi(PSII)) in cucumber leaves. EBR pretreatment alleviated the declines of Pn and Phi(PSII) caused by chlorpyrifos application, and this effect of EBR was associated with reductions of chlorpyrifos residues. To understand how EBR promotes chlorpyrifos metabolism, the effects of EBR on activity and expression of enzymes involved in pesticide metabolism were analyzed. EBR had a positive effect on the activation of glutathione S-transferase (GST), peroxidase (POD), and glutathione reductase (GR) after treatment with chlorpyrifos, although the effect on GR was attenuated at later time points when plants were treated with 1 mM chlorpyrifos. In addition, EBR enhanced the expression of P450 and MRP, which encode P450 monooxygenase and ABC-type transporter, respectively. However, the expression of GST was consistently lower than that of plants treated with only chlorpyrifos. Importantly, the stimulatory effect of EBR on pesticide metabolism was also observed for cypermethrin, chlorothalonil, and carbendazim, which was attributed to the enhanced activity and genes involved in pesticide metabolism. The results suggest that BRs may be promising, environmentally friendly, natural substances suitable for wide application to reduce the risks of human and environment exposure to pesticides.