Abstract: Microsomes were isolated from livers of male Sprague-Dawley rats at 3～4, 14and 24 months of age for each group for the determination of monooxygenase components and drugmetabolism activities. Some GSH-related enzyme activities in microsomes and cytosol were also mea-sured. DPH(1,6-diphenyl-1,3,5-hexatriene) was used to determine the microsomal membrane lipidregion fluidity. Microsomal cytochrome P-450 content and NADPH-cytochrome c reductase activiti-es remained unchanged in old rats, but there were significantly decreases in cytochrome P-450 depen-dent aminopyrine N-demethylase and aniline hydroxylase activities. Glutathione S-transferase (GST)in cytosol and microsomes and glutathione peroxiclase (GSH-Px) in cytosol were also decreased in oldrats. Simultaniously, microsomal membrane fluidity of 24-month old rats decreased (measured at25°C and 37°C), accompanied by an elevation of cholesterol/phospholipid ratio. Results suggest thatthere might be some relationship between the lipid environment and membrane fluidity changes and thedecreases of hepatic biotransformation function.