This study is to correlate the degree of tumor heterogeneity in Apparent Diffusion Coefficient (ADC) at baseline with chemotherapeutic response in bladder cancer patients. MRIs of twenty muscle-invasive bladder cancer patients were performed with Diffusion weighted MRI (DWI). Freehand ROIs were placed on the whole tumor volume on ADC maps to obtain a dataset of voxel-wise ADC values for each patient. Histogram analysis was performed on each patient’s ADC dataset to calculate uniformity (U) and entropy (E) at baseline. These quantities were then correlated with the patient’s chemotherapeutic response. Our data showed that there was a strong correlation of tumor heterogeneity, which is characterized by U and E, and the patient’s chemotherapeutic response. While U was significantly higher, E was significantly lower in responders (both P<0.01) compared to non-responders. In conclusion, quantification of tumor ADC heterogeneity can provide useful information that enables the ability to predict chemotherapeutic response prior to the treatment, to improve the patient outcomes.