It is known that the metabolism of some drugs is altered in diabetic patients and in rats with experimental diabetes induced by chemical agents, such as streptozocin. The induction and/or suppression of hepatic cytochrome P450 isozymes seen in diabetes seem to contribute to this alteration. Both metabolic and hormonal disturbances following insulin deficiency in diabetic rats are responsible for these changes. Marked changes in hepatic P450 isozymes in diabetic rats include increases in the isozymes induced by ketones and lipids, including fatty acids, and decreases in the isozymes regulated by growth hormone and testosterone. Suppressed secretion of thyroid hormones also participates in the mechanism causing these changes. Analysis of cytochrome P450 isozymes in diabetic rats is helpful in elucidating the impaired metabolism of some endogenous substrates catalyzed by the cytochrome P450, such as steroid hormones and fatty acids, in diabetes. The results of these analyses also provide insight into the prescription of drugs for diabetic patients.