This study aimed to investigate the association of thigh muscle fat infiltration by quantitative MRI with muscle strength in patients with type 2 diabetes mellitus (T2DM). Seventy T2DM patients and sixty control subjects (71 males; age: 52 ± 8 years) underwent 3.0T MRI and isokinetic muscle strength measurements to obtain the skeletal muscle index (SMI), intermuscular adipose tissue (IMAT) proton density fat fraction (PDFF), intramuscular fat (IMF) PDFF, peak torque (PT) and total work (TW) of knee extensors and flexors. The differences of measurements between T2DM patients and asymptomatic volunteers were compared. Multivariate regression analysis was used to determine significant predictors of thigh extension and flexion strength. The SMI, IMAT and IMF PDFF of thigh muscles in T2DM patients were higher than that in the control group (p < 0.001), while PT and TW were lower than those in the control subjects (p < 0.05). Both IMF and IMAT PDFF were negatively correlated with PT, TW in participants with T2DM (extensors: r = - 0.72, - 0.70, p < 0.001; r = - 0.62, - 0.56, p < 0.05. flexors: r = - 0.37, - 0.43, p < 0.05; r = - 0.39, - 0.46, p < 0.05). Moderate and strong correlations between HOMA-IR and muscle strength measurements, muscle PDFFs were observed in extensors and flexors. IMF PDFF and age were the statistically significant predictor of PT and TW of extensors of thigh in multivariate regression analysis. Therefore, the thigh muscle PDFF increased was associated with muscle strength decreased in T2DM patients beyond SMI. Age are also important factors influencing thigh muscle PDFF and strength in T2DM patients.© 2023. The Author(s).