OBJECTIVE: To explore the performance of neurite orientation dispersion and density imaging (NODDI) in grading gliomas and to evaluate the cellular proliferation. METHODS: NODDI and diffusion-weighted imaging were performed on 79 patients with histopathologically proven gliomas. Parameter maps of intracellular volume fraction (ICVF), orientation dispersion index (0D1), and apparent diffusion coefficient (ADC) were calculated. Regions of interest were placed in the most solid part of the tumor. These metrics were normalized to the contralateral normal-appearing white matter and correlated with Ki-67 expression. RESULTS: ICVF and ODI increased as tumor grades increased, whereas ADC decreased with the increase of tumor grades. Significant differences in normalized ICVF and ODI were observed between low-grade gliomas and high-grade gliomas (ICVF: 0.208 +/- 0.104 vs. 0.718 +/- 0.234; ODI: 0.952 +/- 0.428 vs. 1.767 +/- 0.636, P < 0.001, respectively) and between grades II and III (ICVF: 0.208 1 0.104 vs. 0.603 1 0.253; ODI: 0.952 +/- 0.428 vs. 1.762 +/- 0.542, P < 0.001, respectively). Normalized ICVF was also significantly different between grades III and IV (0.603 +/- 0.253 vs. 0.803 +/- 0.182, P = 0.004). Ki-67 labeling index was positively correlated with normalized ICVF and ODI (r = 0. 755 and 0.572, P < 0.001, respectively), and negatively correlated with normalized ADC (r = - 0.709, P < 0.001). CONCLUSIONS: NODDI is a promising method in grading gliomas and predicting cellular proliferation. These results may be of great significance for the clinical diagnosis and treatment of gliomas.