In the recent time, several in vitro and in vivo studies have shown the inhibitory effect of grapefruit juice on metabolism of xenobiotics catalyzed by liver oxidative enzymes including cytochrome P450 izoenzymes. However, all these experiments were done with a single dose of grapefruit juice. The primary aim of this study was to evaluate if the chronical ingestion of grapefruit juice can cause enzyme activity alteration as well as a single dose. Three groups of male mice were used: the control group, the group which was administered 0.2 mL of grapefruit juice per os 10 days and the group which was administered single dose of 0.5 mL grapefruit juice per os 90 min. before the sacrificing. After the sacrificing of animals, liver was homogenized with appropriate buffer, and the activity of oxidative liver enzymes: xanthine oxidase (XOD), peroxidase (Px), catalase (CAT), lipid peroxidase (LPx), glutathion peroxidase (GSH-Px) and liver glutathion contents (GSH) were detected by standard methods. The results show that the enzyme activity of liver MFO was changed according to a single or multiple grapefruit juice ingestion. The grapefruit juice in a single oral dose significantly decreases the activity of xanthine oxidase, glutathion peroxidase, lipid peroxidase and liver glutathion contents, and has no effect on activity of catalase and peroxidase. The multiple grapefruit ingestion increases the activity of XOD, GSH-Px, LPx, Px and GSH, while the activity of CAT enzyme is unchanged. The chronical and single grapefruit ingestion has no effect on relative liver weight, but the liver protein content is significantly decreased after the multiple oral grapefruit juice ingestion.