The hypoglycemic effect of extract of Penthorum chinense Pursh (PCP) on a high fat diet and streptozotocin (STZ)-induced diabetic rats was investigated. The efficacy of orally administer PCP (545 mg/kg/day) for 4 weeks were evaluated in high-fat diet and STZ (35mg/kg.) induced diabetic rats, and metformin (500 mg/kg/day) was used as a positive control. A range of parameters, including blood glucose and lipid were tested to evaluate its anti-hyperglycemic effects. Moreover, superoxide dismutase (SOD), malonaldehyde (MDA), glutathione peroxidase (GSH-Px), and catalase (CAT) were performed to determinate their antioxidant activities. The fasting blood glucose and HbAc1 level of PCP treatment group decreased by 43.93% and 77.05%, respectively, when compared with the diabetic rat group (p<0.05). The activities of antioxidant enzymes including GSH-Px, SOD and CAT were significantly improved by 76.32%, 42.75% and 32.12% (p<0.05), respectively. PCP was also found to reduce the levels of MDA (p<0.01). Meanwhile, the histology results showed the extract of PCP could protect against liver and pancreas damages. This study showed that the extract of PCP modulated hyperglycemia in high-fat diet and STZ-induced diabetic rats, which might be attributed to enriching antioxidant enzymes activities.