The goal of the present study is to evaluate the effect of Berberine chloride (BC) on the liver of streptozotocin (STZ) induced diabetic rat. Diabetic rats were treated with BC (50 mg/kg b.w) or glibenclamide (6 mg/kg b.w), daily for 45 days. After BC treatment in diabetic rats, there was a significant (P < 0.05) decline in the levels of hepatic markers, lipid peroxidation markers such as lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS), and pro-inflammatory mediators like tumor necrosis factor-alpha (TNF-α), phosphorylated nuclear factor kappa-B-p65 (phospho-NF-κB p65), cyclooxygenase (COX-2), nitric oxide synthase (iNOS) as well as pro-apoptotic mediators such as Bax and cytochrome c. A significant (P < 0.05) increase in hexokinase, glucose-6-phosphate dehydrogenase, enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and non-enzymatic antioxidants such as glutathione (GSH), vitamin E and vitamin C, as well as anti-apoptotic protein Bcl-2 were observed in the liver of BC treated diabetic rats. Thus, from these findings, it can be concluded that the administration of BC notably recovered the liver from hyperglycemia induced antioxidant imbalance, inflammation and apoptosis as well as rectified the imbalance in carbohydrate metabolizing enzymes.