Diffusion tensor imaging (DTI) is potentially sensitive to collagen degeneration in cartilage. In this study, DTI was measured on human cartilage samples with interventions of trypsin and collagenase. The measured preferred diffusion direction was consistent with the zonal structure of collagen network. The glycosaminoglycan concentration decreased and apparent diffusion coefficient increased with both interventions. The fractional anisotropy (FA) was not affected by trypsin and showed a slight increase with combined trypsin and collagenase intervention. DTI in cartilage is technically challenging due to the low FA and the almost undetectable change with collagen disruption seen here.