Abstract Reliable measurement of glucose in the subcutaneous tissue compartment has been shown to be possible in rats using a miniaturised bipolar enzyme electrode integrated with a unique open microflow strategy in which the sensor surface is subjected to slow, continuous fluid perfusion. Experiments using such a slow, tissue controlled and pumpless perfusion of the implanted needle electrode surface (at a rate of 30 μl/h with chelate containing buffer (EDTA) has been shown to eliminate systematic bias in blood:tissue correlation even under dynamic conditions. Replacement with simple isotonic saline, however, has proved deleterious to sensor performance and reliability yielding a blood/tissue correlation y=0.66 x+2.4, r 2=0.73 (five electrodes). The addition of the vasoconstrictor epinephrine into the saline based perfusion fluid, above a threshold value (0.25 mM), led to a delayed tissue glucose response and further reduced the dynamic correlation with blood ( y=0.31 x+4.31, r 2=0.22, two electrodes). Inclusion of hydrocortisone to saline did not return the original buffer correlation ( y=0.81 x+1.12, r 2=0.79, two electrodes). Preliminary evaluation of open microflow/electrode functionality in non-diabetic human subjects has revealed a contracted stabilisation requirement of 25–35 min, and a reliable correlation with tissue glucose changes with whole blood under dynamic conditions following oral carbohydrate ( y=0.92 x+0.60, r 2=0.97, five electrodes). Reassessment of electrode performance in vitro following a maximal 4 h implantation period demonstrated protected electrode stability with electrode response within 5% of original sensitivity intimating low surface fouling and an eliminated need for repeated in vivo calibration at least over an initial 4 h monitoring period, a highly unstable phase of the operational lifetime of an in vivo electrode.