Objective: To investigate whether normal-appearing brain tissue (NABT) on conventional MRI has occult damage in patients with relapsing-remitting multiple sclerosis (RRMS) by using diffusion tensor imaging (DTI) histogram analysis, and to determine the correlations between DTI histogram-derived measures of the NABT and expanded disability status scale (EDSS) scores, disease durations, T2WI lesion volumes and brain tissue volumes in RRMS patients. Methods: Conventional MRI and DTI scans were performed in 24 patients with RRMS and 24 sex- and age-matched healthy controls. After segmentation of the NABT, the mean diffusivity (MD) and fractional anisotropy (FA) histograms of the NABT were created and analyzed. Results: In patients with RRMS, the average MD (1.014 × 10-3 mm2 · s-1) of the NABT was higher than that (0.910 × 10-3 mm2 · s-1) of control subjects (t = 7.238, P < 0.001); the MD histogram peak height (8.858‰) of the NABT was lower than that (0.767‰) of control subjects (t = 6.161, P < 0.001); the MD histogram peak location (0.809 × 10-3 mm2 · s-1) of the NABT was higher than that (0.767 × 10-3 mm2 · s-1) of control subjects (t = 5.324, P < 0.001); the average FA (0.231) of the NABT was lower than that (0.254) of control subjects (t = 6.217, P < 0.001); the FA histogram peak height (4.502‰) of the NABT was higher than that (4.107‰) of control subjects (t = 4.198, P < 0.001); no significant difference was found in the FA histogram peak location of the NABT between these two groups (t = 1.223, P = 0.227); none of the DTI histogram-derived measures correlated with EDSS scores or disease durations (P > 0.05); the average MD and all the FA histogram-derived measures correlated with T2 WI lesion volumes (P < 0.05); and the average MD, the MD histogram peak height and all the FA histogram-derived measures correlated with brain tissue volumes (P < 0.05). In healthy controls, however, only the average FA of the NABT correlated with brain tissue volumes. Conclusion: Patients with RRMS had occult damage in the NABT and the extent of NABT damage was related to the lesion load of brain and to the extent of brain tissue atrophy.