Urinary oxalate plays an important role in the formation of calcium oxalate stone, and endogenous oxalate metabolism mainly occurs in the liver. Since dehydroepiandrosterone (DHEA) is known to have an effect on hepatocellular proliferation and on some hepatic enzymes, we examined the influence of DHEA on the activity of hepatic oxalate-related enzymes and on urinary oxalate excretion in rats. Fourteen male rats were castrated and divided into two groups. The control group was fed a standard diet, while the other rats were fed a diet containing 0.5% DHEA. After 4 weeks, the liver weight and the urinary levels of oxalate, glycolate, and glycine were significantly higher in the DHEA-treated rats than in the controls, while body weight did not differ between the two groups. Hepatic alanine:glyoxylate aminotransferase and glyoxylate reductase showed significantly higher activity in the DHEA-treated rats than in the controls, while glycolate oxidase activity was significantly reduced. Treatment with DHEA induced hyperoxaluria along with hepatocyte proliferation. This hyperoxaluria was probably caused by hepatocyte proliferation, but it could not be explained simply by the changes of hepatic oxalate-related enzymes. Investigation of the modulation of peroxisomal enzymes by peroxisomal proliferators or inhibitors may provide further insights into hepatocyte oxalate metabolism.