Diabetes mellitus (DM) is a metabolic disease involving improperly high blood glucose level, hyperlipidemia and hypoinsulinemia. The aim of current study is to assess and compare the influence of Quercus infectoria galls (QIg) extract and glimepiride on pancreatic β-cells secretory function and serum lipid profile in diabetic rats. In the present study, thirty six male rats were used and divided into six groups (n=6), including negative control, STZ induced diabetic control, treated diabetic rats with glimepiride (200mg/Kg Bw), and treated diabetic rats with different concentrations QIg extract, 200 mg, 400 mg and 800 mg/Kg Bw for 42 days, respectively. At the end of the experiment, all rats were fasted overnight, blood samples were collected for measuring fasting blood glucose, insulin hormone and lipid profile. All rats were then scarified by using chloroform in order to take part of the pancreatic tissue. The results show a significant decrease in blood glucose, total cholesterol, triglycerides, low density lipoprotein, very low-density lipoprotein, HbA1c% with obvious elevation in serum insulin hormone and high-density lipoprotein in diabetic rats treated with QIg extract and glimepiride compared with diabetic untreated group. In addition, high atherogenic index in diabetic rats was significantly reduced by different concentrations of QIg extract and glimepiride. Histopathogical results revealed that there was a significant and dose-dependent morphological restoration in the pancreatic structure damages especially at high dose of the extract. These findings provide a new insight into the role of QIg methanolic extract in maintaining normal blood glucose and adequate pancreatic insulin hormone secretion in diabetic rats, amelioration of dyslipidemia and associated cardiovascular alterations with subsequent improvement in pancreatic structural damages in diabetic rats.