Background: The inability of the newborn to inhibit gluconeogenesis in response to a glucose infusion leading to insulin resistance has been postulated as an important cause of hyperglycaemia observed in premature infants. Aim: The aim of this study was to determine the efficiency and rate of response to continuous insulin infusion in improving glucose tolerance in hyperglycaemic extremely-low-birth-weight (ELBW) neonates (≤1,000 g) compared to neonates with birth weight >1,000 g (LBW). Methods: We included in the study 115 consecutive neonates in the neonatal intensive care unit who developed hyperglycaemia from January 2000 to December 2001. A standard protocol for the use of exogenous insulin infusions was commenced for all hyperglycaemic neonates. The efficiency of continuous insulin infusion was compared in two groups of infants: ELBW ≤1,000 g compared with neonates with birth weight >1,000 g (LBW). Results: The duration (hours) of insulin infusion required to normalise blood glucose level was significantly longer in the ELBW group compared to LBW group (p < 0.0001). Average insulin infusion (units/kg/h) required to maintain normoglycaemia was also significantly higher in the ELBW group (p < 0.0001). No significant difference was found in the mean amount of intravenous dextrose tolerated, mean postnatal age (hours) at which infusions were initiated and the average blood glucose recorded. ELBW infants were more likely to receive steroid administration, have surgery, higher CRIB scores and sepsis. Conclusion: Continuous insulin infusion was relatively safe and effective in the treatment of persistent hyperglycaemia in premature neonates. No serious adverse side effects of insulin therapy were noted. With the current protocol for use of exogenous insulin infusion at our unit, the response to treatment was significantly slower in the ELBW neonates. The dose of insulin infusion required to maintain normoglycaemia was also higher in this group of neonates. There may be a need for different treatment schedules for this subgroup of neonates so that normalisation of blood glucose can be achieved earlier.