BACKGROUND AND OBJECTIVE: Teucrium polium Lamiaceae. an antidiabetic traditional medicine was observed to stimulate insulin secretion and β-cell mass restoration in pancreatic of diabetic rats. Bioactive compounds in T. polium such as terpenoids and flavonoids have a wide range of antioxidant properties. Given this background, our research was aimed at probing the effective molecular mechanism of T. polium which in turn protects the pancreatic β-cells of diabetic rats through attenuation of streptozotocin-induced oxidative stress. MATERIALS AND METHODS: Induction of diabetes by streptozotocin (STZ) injection followed by treatment of the rats with T. polium extract (0.5g/kg) and glibenclamide as a standard drug (600μg/kg) for six consecutive weeks. Besides, biochemical indexes including sera glucose and lipids were investigated once every two weeks. Moreover, oxidative stress markers were also measured in the sixth week of treatment to assess the antioxidant capacity of T. polium. Prior to sacrifice of rats, the oral glucose tolerance test was carried out and thereafter western blot analysis was performed on pancreatic tissues to detect the expression of JNK, FoxO1 and Pdx1 proteins in the experimental groups. RESULTS: Oral administration of T. polium extract not only disclosed the significant anti-hyperglycemic potential of the plant, but also relieved dyslipidemia and oxidative stress related to diabetes. Furthermore, remarkable improvement of glucose tolerance was exhibited among the treated groups, confirming the presence of insulin in the blood. Subsequently, the effective molecular mechanism of T. polium was partially revealed by western blot analyses which detected considerable up-regulation of p-FoxO1 and Pdx1 proteins parallel to reduction of p-JNK expression among the treated diabetic rats. CONCLUSION: This study demonstrates that T. polium extract is able to restore the β-cell mass and insulin secretion by regulation of pivotal transcription factor of the pancreatic β-cells Pdx1 in JNK pathway.