Overuse activity has been implicated as an etiologic factor in injury to the rotator cuff and to the supraspinatus tendon in particular. Due in part to the lack of an appropriate animal model, experimental studies have not addressed this issue. With the use of a rat model, we measured the effects of an overuse running regimen on 36 Sprague-Dawley rats after 4 (n = 12), 8 (n = 12), or 16 (n = 12) weeks of exercise and compared them with a control group of rats (n = 10) who were allowed normal cage activity. The histologic characteristics, the gross morphologic characteristics, and the mechanical properties of the tendon tissue were evaluated. The supraspinatus tendons in the exercised animals demonstrated significant changes as a result of overuse at all time points compared with the normal group. There was an increase in cellularity and a loss of the normal collagen fiber organization consistent with what has been seen in human tendinopathy. The tendons from the exercise groups were larger than normal in cross-sectional analysis at 4 weeks (129% of control, P <.01) and continued to increase in size with time to 16 weeks (164% of control, P =.01). The mechanical properties of the tendons deteriorated in response to overuse exercise with a decreased modulus of elasticity ranging from 52% to 61% of control (P =.07 at 4 weeks, P <.05 at 8 and 16 weeks) and a decreased maximum stress at failure ranging from 51% to 63% of control (P <.007). These findings support overuse activity as an etiologic factor in the development of supraspinatus tendinopathy and begin to describe the changes in the tendons as a result of such activity. This model can now be used to study the effect of various treatment modalities on these injuries.