We examined whether Nigella sativa (NS) oil and its active constituent thymoquinone (TQ) attenuate oxidative stress in the heart and brain in an experimental model of diabetes mellitus using streptozotocin (STZ). Oxidative stress was assessed by measuring cardiac and brain nitric oxide (NO), lipid peroxide levels, glutathione (GSH) and antioxidant enzyme activities, i.e. glutathione-S-transferase (GST) and catalase. Cardiac metabolic damage was estimated by measuring cardiac creatine kinase muscle and brain types (CK-MB). Brain monoamine levels were also evaluated. STZ diabetes induced a significant increase in heart and brain NO and malondialdehyde concentrations compared with the control group. These changes were attenuated by posttreatment of rats with NS oil and TQ. STZ diabetes induced oxidative stress via a significant decrease in GST, GSH and catalase. These lowered levels were improved by either NS oil or TQ administration. Serum CK-MB was decreased in the diabetic rats, which recovered with NS oil and TQ administration. During the course of diabetes, there was a marked increase in norepinephrine and dopamine concentrations and a marked decrease in serotonin concentration compared to the control group. These findings were partly reversed by oral administration of either NS oil or TQ. It is concluded that NS and TQ correct STZ-diabetes-induced alterations in CK-MB and brain monoamines due to their antioxidant properties.