This study compares the effects of glibenclamide and creatine in type II diabetics. In a 14-day symmetrically randomized crossover trial recently detected type II diabetics received either creatine (3 g) or glibenclamide (3.5 mg) for five successive days, followed by two days of washout, and crossover to the opposite treatment. Glucose, insulin, c-peptide, and creatine were measured. Creatine and glibenclamide decreased glucose concentrations vs. basal glucose [-15, 60, 90, 120, 180, and 240 min; mol/l]: 12.6±0.83 vs. 12.2±0.56 vs. 12.1±0.57, 15.3±0.63 vs. 13.5± 0.70(a ) vs. 13.0±0.57(a), 14.8±0.57 vs. 13.8±0.59(a) vs. 13.4±0.46(a), 14.6±0.61 vs. 12.3±0.49(b) vs. 12.4±0.61(a), 12.8±0.76 vs. 10.0± 0.40(c) vs. 10.3±0.41(c), and 11.4±0.67 vs. 8.3±0.40(c) vs. 8.5±0.36(c); ((a) p<0.05; (b) p<0.01; (c) p<0.001 vs. basal glucose). Treatment with both creatine and glibenclamide increased insulin and c-peptide concentrations after 120 and 240 min (p<0.05 and p<0.01). At the doses applied short-term treatment with creatine and glibenclamide elicits similar glucose lowering effects.