The apparent diffusion coefficient (ADC) of extravascular tissue water in rat brains was measured in response to step-wise injections of the superparamagnetic intravascular contrast agent AMI-227. These data were normalized and compared with measured changes in R2* and blood magnetic susceptibility. Linear regression showed that ADC changes 33%/ppm shift of intravascular susceptibility and 0.43% s(-1) change in R2*. These changes correspond to a predicted ADC change of approximately 6% for a change between fully oxygenated and fully deoxygenated blood. The source of these ADC changes was confirmed to be background gradients within the sample by the use of diffusion weighting with bipolar gradients of odd symmetry designed to cancel such background gradient effects on ADC. The results suggest that diffusion-weighted imaging is sensitive to blood-oxygenation and may provide a means of measuring changes in blood oxygen. They also provide estimates of the potential contribution of susceptibility changes to changes in ADC that occur, for example, in stroke and seizure.