The role played by glucose and/or insulin in local vascular regulation of tissue glucose uptake is largely unknown. Thus, the aim of this study was to examine microvascular changes induced either by hyperinsulinaemia alone or in combination with hyperglycaemia. The effects of insulin or glucose on the diameter and periodic vasomotion of precapillary arterioles (diameter < 20 microm) were determined by using the spinotrapezius muscle preparation in fasted, anaesthetized rats. Ten minutes after s.c. insulin administration, the blood insulin level was greatly increased whereas plasma glucose remained unchanged. This was associated with a marked and durable vasodilation of terminal arterioles without significant changes in vasomotion. When similar plasma insulin levels were attained by glucose infusion, tissue glucose uptake was increased in spite of a partial constriction and increased vasomotion of precapillary arterioles. Importantly, local tissue blood flow was not reduced despite the diminution in microvascular diameters. These results indicate that hyperinsulinaemia alone produces an increase in the diameter of terminal arterioles. This effect seems to be offset when the same level of hyperinsulinaemia is associated with hyperglycaemia (such as occurs postprandially), as illustrated by vasoconstriction of the muscle terminal arterioles. Our data suggest that the vasoconstriction of precapillary arterioles may be part of an active regulation for optimal glucose supply to the tissue in acute hyperglycaemic episodes. These data provide the first direct evidence that insulin and glucose can act as regulators of microflow in the skeletal muscle, as illustrated by changes in precapillary haemodynamics.