Abstract Disclosure: H. Park: None. E. Oh: None. S. Park: None. H. Kim: None. D. Byun: None. Magnetic resonance imaging (MRI) has played little role for the study of peripheral nerve disease. However, recent technological advances in MRI have provided us more information about neural microstructure and higher resolution in peripheral nerves. The aim of this study is to evaluate whether diffusion tensor imaging (DTI) parameters in MRI can detect peripheral neuropathy in type 2 diabetes (T2D). In this prospective, single-center study, eight T2D patients (mean age, 62.1 ± 10.8 yr; 5 M/ 3F) with peripheral neuropathy and seven healthy controls (65.0 ± 3.3 yr, 7 F) were included. All T2D patients underwent Michigan Neuropathy Screening Instrument questionnaire and quantitative sensory testing. MRI including DTI and axial T2-weight Dixon sequence was performed for each participant. Region of interest analysis was independently performed by one radiologist on each side of tibial nerve at two levels: lower margin of adductor magnus muscle insertion (level 1), and quadriceps femoris tendon at patellar attachment (level 2). DTI parameters including cross-sectional areas (CSA), fractional anisotropy (FA), as well as diffusivity (mean (MD), axial (AD), and radial (RD)) were calculated. FA was significantly lower in T2D patients with peripheral neuropathy than healthy controls at both level 1 (396 ± 74 vs. 541 ± 141, P<0.05) and level 2 (422 ± 65 vs. 565 ± 108, P<0.05). AD was significantly lower in T2D patients with peripheral neuropathy than controls at level 2 (2,207 ± 492 vs. 2,884 ± 497, P<0.05). RD was significantly higher in T2D patients with peripheral neuropathy than controls at level 1 (1,156 ± 313 vs. 867 ± 147, P<0.05). No difference in the CSA of the tibial nerve was seen in both levels between two groups. Our results have shown that DTI parameters can detect nerve abnormalities of the tibial nerve in T2D patients, suggesting DTI may be useful as a biomarker in diabetic peripheral neuropathy. Presentation: Thursday, June 15, 2023