Introduction: Sonophoresis has been assessed as a novel approach to create skin permeability and drug delivery using low frequencies of ultrasound waves in the range of 20 kHz to 3 MHz. In this study, a system including seven 40 kHz piezoelectric transducers and an insulin chamber designed by the Medical Physics Research Center has been evaluated on hyperglycemic rabbits. Materials and Methods: Thirty five rabbits became hyperglycemic through Alloxan monohydrate injection and were divided into five groups. The rabbits were treated in two main groups (with insulin and ultrasound radiation in two radiation periods), one main control group and two further control groups (one group with ultrasound radiation with longer radiation period in absence of insulin and presence of normal saline; and the other group without ultrasound radiation in presence of insulin). By filling the system chamber with insulin and placing it on the skin of the abdomen and activating the piezoelectric transducers, blood samples were drawn from the animals before ultrasound irradiation and after it in specified intervals. The glucose level was measured using a glucometer and the serum insulin level was determined using a radioimmunoassay method. Results: Maximum decrease in glucose level was recorded for a 20 minute irradiation in a 180 minute period, and the highest increase in insulin level was recorded for the10 minute radiation group in a 60 minute period. Discussion and Conclusion: Because rapid uptake and reaching a peak in a short time and its swift decrease make a good scheme for controlling glucose level after meals, the 10 minute radiation seems to be more suitable. Also, it is predicted that irradiation time in the interval between food consumption and use of the instrument is critical