There is considerable evidence to suggest that electrical stimulation (ES) activates glucose uptake in rodent skeletal muscle. It is however unknown whether ES can lead to similar metabolic enhancement in humans. We employed low-frequency ES through surface electrodes placed over motor points of quadriceps femoris muscles. In male subjects lying in the supine position, the highest oxygen uptake was obtained by a stimulation pattern with 0.2 msec-biphasic square pulses at 20 Hz and a 1 sec on-off duty cycle. Oxygen uptake was increased by approximately 2-fold throughout the 20 min stimulation period and returned to baseline immediately after stimulation. Concurrent elevation of the respiratory exchange ratio and blood lactate concentration indicated anaerobic glycogen breakdown and utilization during ES. Whole body glucose uptake determined by the glucose disposal rate (GDR) during euglycemic clamp was acutely increased by 2.5 mg/kg/min in response to ES, and moreover, remained elevated by 3-4 mg/kg/min for at least 90 min after cessation of stimulation. Thus, the stimulatory effect of ES on whole body glucose uptake persisted not only during but also after stimulation. Low-frequency ES may become a useful therapeutic approach to activate energy and glucose metabolism in humans.