Purpose To evaluate differences in diffusion imaging parameters, including fractional anisotropy (FA) and the apparent diffusion coefficient (ADC), in control and diabetic subjects, and to assess changes in these parameters to patient’s urine albumin/protein levels, estimated glomerular filtration rate (eGFR), and glycated haemoglobin (HbA 1c ). Material and methods This is a cross-sectional analytical study involving 100 patients who underwent diffusion imaging including diffusion tensor imaging (DTI) of the kidneys in our hospital from 2019 to 2020. Diffusion imaging parameters (ADC and FA) were obtained from the medulla and cortex of both kidneys using dedicated software. Statistical analysis was done. Results Out of 100 subjects, 27 were controls and 73 were diabetics (19 normoalbuminuric, 23 microalbuminuric, and 31 proteinuric). The medullary FA (0.419 ± 0.024 vs. 0.346 ± 0.042), cortical FA (0.194 ± 0.035 vs. 0.303 ± 0.067), and cortical ADC (3.307 ± 0.341 vs. 2.309 ± 0.515) values showed significant differences between controls and diabetics. Medullary FA and cortical ADC values showed a decreasing trend with an increasing amount of albumin/protein in the urine, decreasing renal function (reducing eGFR), and increasing HbA 1c , whereas the trend was opposite for cortical FA. In addition, on ROC curve analysis a cut-off value for medullary FA of 0.4 had a sensitivity of 64% and specificity of 80.95% to differentiate healthy volunteers and diabetics with normo-albuminuria. Conclusions DTI has the potential to be a promising non-invasive test for the detection of early renal parenchymal changes in diabetic nephropathy.