The optimum pharmacological treatment of type 2 diabetes mellitus (DM2) in youth for those who fail to achieve adequate glycemic control (HbA1c <7%) with lifestyle intervention is unknown. The aim of this pilot study was to observe the effect of short-term insulin therapy (<16 weeks duration) on glycemic control in youth with DM2. A pre-mix 30/70 insulin was given twice daily to 18 youth aged 10-18 years with DM2 for 8.7+/-4.3 weeks with a starting dose of 0.5 U/kg/day. HbA1c, body mass index (BMI) and episodes of hypoglycemia were monitored during the treatment period and for a 12-month period after insulin was stopped. Mean HbA1c decreased from 12.81% to 7.59% (95% CI 6.54, 8.64). This improvement persisted for 12 months without any further drug therapy. There was no significant change in mean BMI and there were no episodes of moderate or severe hypoglycemia. Decreasing beta-cell glucose toxicity with rapid improvement of blood glucose may play an important role in treatment of DM2 in adolescents. Early success in achieving target blood glucose levels is an important aspect of adolescent DM2 care.