Diabetes mellitus (DM) is a spectrum of metabolic disorders, arising from pathologic mechanisms, resulting in hyperglycaemia. Diabetes and hypertension frequently occur together and are leading risk factors for cardiovascular complications. This study examined the effects of amlodipine and valsartan on glibenclamide-treated streptozotocin-induced diabetic rats. Male albino rats (200-350 g) were fasted overnight and DM was induced by a single dose 40 mg/kg of streptozotocin (i.p.). After 48 h, DM was confirmed (blood sugar ≥200 mg/dl) and the animals were grouped into normal rats with no drug treatment, untreated diabetic animals and groups treated with glibenclamide, glibenclamide plus amlodipine, and glibenclamide plus valsartan. After six weeks treatment, animals were sacrificed under chloroform anaesthesia. Kidney, liver, lung, heart and blood were collected for histology, haematological and biochemical analyses. Untreated diabetic rats had 100% mortality before 6 weeks but addition of valsartan to glibenclamide improved survival rate (71.4% compared with 57.4% in glibenclamide-treated) and blood glucose control but this was not so with glibenclamide plus amlodipine-treated group with 50% survival rate. Treatment ameliorated pathologic changes and there was histologic evidence of organ protection among the various treatment groups when compared with the untreated diabetic group. Addition of valsartan to glibenclamide improved treatment outcome compared to when glibenclamide was used alone but this was not so with the addition of amlodipine to glibenclamide.