Berberine chloride (BC) has been widely used as an unprescribed oral drug in China for the treatment of various diseases, and it is an active ingredient in many traditionally used medicinal plants. The present study was undertaken to evaluate the beneficial effects of BC on oxidative stress, inflammation and apoptosis in the pancreas of Streptozotocin (STZ) induced diabetic rats. Diabetes was induced in the male Wistar albino rats using a single intraperitoneal injection of STZ of 40mg/kg b.w. Diabetic rats were treated with BC (50mg/kg b.w) for 45days. Oral administration of BC showed significant reduction of the blood glucose, glycated hemoglobin (HbAlc) and increased the plasma insulin, hemoglobin (Hb) and body weight. Lipid peroxidation marker LOOH and TBARS levels were reduced while SOD, CAT, GPx, GSH, vitamin E and vitamin C levels were increased in the pancreas. A significant reduction of pro-inflammatory mediators (TNF-α, NF-κB, phospho-NF-κB-p65, COX-2 and iNOS) and pro-apoptotic proteins (caspase-8, t-Bid, Bax, cytochrome-c and cleaved caspase-3), and elevation of anti-apoptotic protein Bcl-2, anti-inflammatory mediator IL-10 and GLUT-2 in were observed in BC treated diabetic rats. Thus, the present study demonstrated that BC has anti-hyperglycemic, antioxidant, anti-inflammatory and anti-apoptotic activities in STZ induced diabetic rats.