Background: Diabetes mellitus is associated with biochemical and pathological alterations in the liver. The aim of this study was to investigate the effects of apple cider vinegar (ACV) on serum biochemical markers and histopathological changes in the liver of diabetic rats for 30 days. Effects were evaluated using streptozotocin (STZ)-induced diabetic rats as an experimental model. Materials and methods: Diabetes mellitus was induced by a single dose of STZ (65 mg/kg) given intraperitoneally. Thirty wistar rats were divided into three groups: control group, STZ-treated group and STZ plus ACV treated group (2 ml/kg BW). Animals were sacrificed 30 days post treatment. Results: Biochemical results indicated that, ACV caused a significant decrease in glucose, TC, LDL-c and a significant increase in HDL-c. Histopathological examination of the liver sections of diabetic rats showed fatty changes in the cytoplasm of the hepatocytes in the form of accumulation of lipid droplets, lymphocytic infiltration. Electron microscopic studies revealed aggregations of polymorphic mitochondria with apparent loss of their cristae and condensed matrices. Besides, the rough endoplasmic reticulum was proliferating and fragmented into smaller stacks. The cytoplasm of the hepatocytes exhibited vacuolations and displayed a large number of lipid droplets of different sizes. On the other hand, the liver sections of diabetic rats treated with ACV showed minimal toxic effects due to streptozotocin. These ultrastructural results revealed that treatment of diabetic rats with ACV led to apparent recovery of the injured hepatocytes. In prophetic medicine, Prophet Muhammad peace is upon him strongly recommended eating vinegar in the Prophetic Hadeeth: "vinegar is the best edible". Conclusion: This study showed that ACV, in early stages of diabetes induction- can decrease the destructive progress of diabetes and cause hepatoprotection against the metabolic damages resulting from streptozotocin- induced diabetes mellitus.