This study was designed to assess the diagnostic value of quantitative diffusion-weighted (DW) and intravascular micro-imaging magnetic resonance imaging (IVIM)-derived DW metric values predictive for hypoxia-inducible factor-1α (HIF-1α)+ clusterofdiffe-rentiation31(CD31)/microvascular density(MVD) levels in a nude mouse model with breast cancers. Quantitative parameters for apparent diffusion coefficient (ADC), the diffusion components including D and pseudodiffusion, known as fraction with free water (D*), were derived from fitting results of a breast cancer model in 33 nude mice. Immunohistochemistry was performed to analyze HIF-1α and MVD levels using CD31. The associations of these variables with pathological features were evaluated. The diagnostic performance of quantitative imaging indices was evaluated by the Area Under Receiver Operating Characteristic Curve (AUC) and Intra-class Correlation Coefficient (ICC). Conclusion: DWI quantitative parameters, especially the D and ADC values from IVIM-DWI, are helpful for evaluating hypoxia in the tumor microenvironment and MVD of tumors.