OBJECTIVE: To characterize structural changes and the metabolic profile of foot muscles and correlate them with diabetic neuropathy measurements using phosphorus-31 ((31)P) rapid acquisition with relaxation enhancement (RARE) magnetic resonance imaging (MRI). RESEARCH DESIGN AND METHODS: We studied 12 control subjects, 9 non-neuropathic diabetic patients, and 12 neuropathic diabetic patients using (31)P RARE and proton ((1)H) MRI at 3 Tesla. The ratio of the total cross-sectional area of the foot to that of the muscle tissue was calculated from transaxial (1)H and (31)P images. The average (31)P concentration across the metatarsal head region was measured from the (31)P images. RESULTS: The muscle area-to-total area ratio differed among all three groups (means +/- SD): 0.55 +/- 0.04 vs. 0.44 +/- 0.05 vs. 0.06 +/- 0.06 for control, non-neuropathic, and neuropathic subjects, respectively (P < 0.0001). The average (31)P concentration also differed among all groups: 27.7 +/- 3.8 vs. 21.7 +/- 4.8 vs. 7.9 +/- 8.8 mmol/l for control, non-neuropathic, and neuropathic subjects (P < 0.0001). The muscle area-to-total area ratio strongly correlated with clinical measurements: Neuropathy Disability Score, r = -0.83, P < 0.0001; vibration perception threshold, r = -0.79, P < 0.0001; and Semmes-Weinstein monofilaments, r = -0.87, P < 0.0001. CONCLUSIONS: Small muscle atrophy is present in diabetes before clinical peripheral neuropathy can be detected using standard clinical techniques. The (31)P RARE MRI method evaluates the severity of muscle atrophy, even in the early stages when neuropathy is absent. This technique may prove to be a useful diagnostic tool in identifying early-stage diabetic foot problems.