Pancreatic cancer is a devastating disease with poor prognosis. Pancreatic tumor therapy has been ineffective in part because pancreatic tumors have high interstitial fluid pressure (IFP), driven by high hyaluronan concentration, that inhibits penetration of drugs into the tumor. We performed multi-parametric MRI at high resolution to non-invasively assess tumor response in a KPC mouse model to pegylated recombinant hyaluronidase in isolation as well as combined with Gemcitabine. T1 and T2 relaxation as well as diffusion, and 3 dimensional volume measurements were used to characterize the tumors. MR measurements were compared with invasive IFP measurements and histopathological results.