We demonstrated previously that in healthy young men 5-aminoimidazole-4-carboxamide 1--D-ribofuranoside (AICAR) stimulates human muscle 2-deoxyglucose (2DG) uptake without detectable activation of muscle AMP-activated protein kinase (AMPK) but with extracellular-regulated kinase 1/2 (ERK1/2) activation. We tested whether AICAR stimulates muscle 2DG uptake in healthy older patients with or without type 2 diabetes (T2D). 6 healthy young (23 ± 3 y, BMI 25 ± 2 kg.m^-2; means ± SEM), 8 older (59 ± 4 y, BMI 28 ± 2 kg.m^-2) and 8 subjects with T2D (62 ± 4 y, BMI 27± 2 kg.m^-2) received a 6 h 2DG infusion (prime 10 mg.kg^-1; 6 mg.kg^-1.h^-1), and AICAR (10 or 20 mg.kg^-1.h^-1) from 3-6 h. Quadriceps biopsies were taken at 0, 3 and 6 h. We determined, i) 2DG uptake, ii) total AMPK activity, AMPK, ACC and AS160 phosphorylation, and iii) ERK1/2 phosphorylation. 10 mg.kg-1.h-1AICAR increased 2DG uptake by 2.9 ± 0.7 fold in young men (P<0.001), 1.8 ± 0.2-fold in older men (P<0.01) and 1.6 ± 0.1-fold in men with T2D; 20 mg.kg-1.h-1AICAR increases were 2.5 ± 0.1 fold (older men, P<0.001) and 2.2 ± 0.2 fold (men with T2D, P<0.001). At 3 h AMPK activity and AMPK, acetyl CoA carboxylase (ACC) and AS160 phosphorylation were unchanged but ERK1/2 phosphorylation increased at both AICAR doses. The fold changes of ERK1/2 phosphorylation and 2DG uptake closely correlated (R²= 0.55; P=0.003). AICAR stimulates muscle 2DG uptake in T2D to the same extent as in healthy age-matched controls but there is an age-related reduction.