Articular cartilage is a thin complex tissue that covers the bony ends of joints. Changes in the composition and structure of articular cartilage will cause degeneration, which may further lead to osteoarthritis. Decreased stiffness is one of the earliest symptoms of cartilage degeneration and also represents the imperfect quality of repaired cartilage. An optical coherence tomography (OCT)-based air-jet indentation system was recently developed in our group to measure the mechanical properties of soft tissues. In this study, this system was applied to quantify the change of mechanical properties of articular cartilage after degeneration induced by enzymatic digestions. Forty osteochondral disks (n = 20 × 2) were prepared from bovine patellae and treated with collagenase and trypsin digestions, respectively. The apparent stiffness of the cartilage was measured by the OCT-based air-jet indentation system before and after the degeneration. The results were also compared with those from a rigid contact mechanical indentation and an ultrasound water-jet indentation. Through the air-jet indentation, it was found that the articular cartilage stiffness dropped significantly by 84% (p 0.8, p