Although it was proved that peroxovanadate-nicotinic acid (POV) can decrease hyperglycaemia and hyperlipaemia, its molecular biochemical mechanism of action is unclear The present investigation aimed at studying the effect of POV on gene expression and enzymatic activity of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and blood lipid metabolism in streptozotocin-diabetic rats in order to suggest the molecular biochemical mechanism of POV action in lowering hyperglycaemia and hyperlipaemia. The results showed that the gene expression and enzymatic activity of hepatic cytosolic PEPCK, which were increased in diabetic rats, were significantly reduced following POV treatment, Similarly, POV was shown to oppose significantly the hyperglycaemia and hyperlipaemia in these diabetic rats. These results suggested that a possible mechanism of POV action was to inhibit PEPCK gene expression as well as PEPCK activity which could explain the reduced gluconeogenesis and hyperglycaemia.