Biopotential, the electric potential generated by living tissues, is affected by changes in extracellular electrolyte and glucose concentrations. We aimed to apply correlation between blood glucose concentrations (BGC) and biopotential of peripheral muscles for noninvasive blood glucose measurement. The study included 58 Wistar rats. In part of them, diabetes was induced by streptozotocin injection. Group 1, comprising 19 normal and 5 diabetic rats, received glucose-challenging protocol (intraperitoneal injection of 1 g/ml glucose). Group 2, 24 normal and 6 diabetic rats, received insulin-challenging protocol (three 30 IU insulin injections with 15-min intervals). Four control rats, group 3, were injected with 2-ml saline. BGC were measured by a standard ACCU-CHEK-Sensor Meter and compared with those estimated by biopotential sensor, further designated as GlucoSat, placed around proximal parts of the tails of the anaesthetized animals. GlucoSat results were calculated using the following biopotential equation: BGC(t) = k1 F1(t) + k2 F2(t) k3 F3(t) + k4, based on an experimental model involving estimation of pH, muscle metabolism, and tissue conductance, where t is time, k1-k4 are coefficients, and F1-F4 are functions. Mean biopotential system measured BGC was 181.7 +/- 4.3 mg/dl, not differing statistically from 187.9 +/- 4.3 mg/dl estimated by ACCU-CHEK. Pearson's correlation coefficient (r(2)) was 0.961 (P < 0.00001), indicating strong, direct correlation between the results. Within the nondiabetic group, r(2) was 0.944 (P < 0.00001), while, within the diabetic group, r(2) was 0.974 (P < 0.00001). No significant, adverse skin reactions were concomitantly observed in any experimental group. Biopotential measurements may be used for continuous, noninvasive estimation of changes in BGC. Further studies are needed to evaluate the applicability of this method to humans.