Abstract: Objective：To explore the effects of pioglitazone on the cytochrome P450 in the liver microsomes of the diabetic rats. Methods：Forty rats were randomly divided into four groups (n=10 in each group): normal control group, diabetes model group, 3 mg/kg and 6 mg/kg pioglitazone groups. Except the normal control, all other groups were fed with high-fat diet for 4 weeks, and then diabetic model rats were established by intraperitoneal injection with streptozotocin (STZ) of 50 mg/kg once. After modeling, rats in the pioglitazone groups were continuously intragastric administrated with pioglitazone for 2 weeks, and then sacrificed and the liver microsomes were extracted for the assay of P450. Meanwhile, the blood glucose and body weight were measured. Results：Compared with the normal control, the blood glucose in the diabetes model group increased significantly (P<0.01), the expression of cytochrome P450 also significantly increased (P<0.05), and body weight significantly decreased (P<0.01). Compared with the diabetes model group, during the 2 weeks of gavage, with the increasing of pioglitazone dose, the blood glucose in pioglitazone groups decreased remarkably (P<0.01), and the expression of cytochrome P450 obviously decreased in the two pioglitazone groups (P<0.01), whereas the body weight increased (P<0.05). In addition, the correlation analysis showed that there was a significantly positive correlation between cytochrome P450 and blood glucose in rats and the correlation coefficient was 0.598 (P<0.01). There was no significant correlation between cytochrome P450 and body weight in rats. Conclusions：Pioglitazone could inhibit the activity of cytochrome P450 in the liver of diabetic rats, reduce the blood glucose, and increase body weight in diabetic rats.