AimTo establish rat model of insulin resistance，then treated by related drugs and to observe the expression of Caspase-3 in renal tissue, which was to investigate the relationship between amount of expression of Caspase-3 and extent of insulin resistance.MethodsThe insulin resistant model of neonatal Wistar rats was induced by a single intraperitoneal injection of streptozotocin(STZ) at a dose of 100 mg/kg.The Wistar rats were divided into four groups, including: normal control(control group),insulin resistance(IR group ), the metformin (metformin group ) and the combinated treatment of tetramethylpyrazine and aminoguanidine(combinated treatment group).The concentrations of fasting blood glucose(FPG), fasting insulin (FIN) and insulin resistance index(IRI)were measured on the eighth and thirty-second week.At the end of thirty-second week， one kidney of each rat was localized for 24 hours using 4% paraformaldehyde, embedded in the paraffin and made into 5um section.Another one was quickly frozen by liquid nitrogen, then stored at -80℃.IHC and western-blot were respectively used to qualitatively and quantitatively evaluate expression of Caspase-3.Results (1) The insulin resistance index in IR group was significantly higher than in control group（p<0.01）. metformin and combinated treatment groups were remarkably lower than IR group (p<0.01); and combinated treatment group was less than metformin group (p<0.05).(2)The alteration of Caspase-3: IR group was obviously higher than control group(p<0.01), metformin and combinated treatment groups were evidently lower than IR group(p<0.01), and combinated treatment group was lower than metformin group (p<0.05).ConclusionThe method of intraperitoneal injection of Streptozotocin can induce insulin resistance in neonatal Wistar rats; In this induced model the concentration of Caspase-3 increased, and there is a positive correlation between up-regulation of Caspase-3 and insulin resistance; metformin and the combined treatment with tetramethylpyrazine and aminoguanidine improved streptozotocin-induced insulin resistance via a mechanism of reducing Caspase-3 expression, furthermore the combination treatment of tetramethylpyrazine and aminoguanidine surpassed single metformin treatment at this aspect.