We previously demonstrated that exposure of spontaneously hypertensive rats (SHR) to dietary doses of sulforaphane (SF) results in resisting the progressive rise in blood pressure that is normally seen in these rats. This study investigates the potential effect of SF on hepatic drug metabolizing enzymes (DME) in SHR. The activity and/or protein expression of selected cytochrome P450 (CYP) enzymes and microsomal epoxide hydrolase (mEH) were measured in hepatic microsomes using specific probe substrates and/or polyclonal antibodies. Cytosolic fraction was utilized to measure protein level and activity of major antioxidant systems. The high dose SF resulted in a significant reduction of activity and apoproteins level of CYP1A2 and CYP2C9 and activities of CYP2B1/2 and mEH. No effect of SF was observed on the rest of the studied CYP enzymes. Both doses of SF resulted in a significant induction of both hepatic glutathione level and activities of superoxide dismutase and catalase. Activities of hepatic glutathione-S-transferases, glutathione reductase, and glutathione peroxidase were significantly induced only with the high dose. This study demonstrates that dietary doses of SF modulate the activity or protein expression of DME. Additionally, induction of the impaired antioxidant system in SHR may explain the blood pressure lowering effect of SF in this rat model. Copyright © 2015 John Wiley & Sons, Ltd.