BACKGROUND: After surgical repair of chronic rotator cuff tears, healing of the repaired tendons often fails and is accompanied by high-level fatty degeneration. Our purpose was to explore the effects of polydeoxyribonucleotide (PDRN) and polynucleotide (PN) on tendon healing and the reversal of fatty degeneration in a chronic rotator cuff tear model using a rat infraspinatus. METHODS: Sixty rats were randomly assigned to the following three groups (20 rats per group: 12 for histological evaluation and 8 for mechanical testing): saline + repair (SR), PDRN + repair (PR), and PN + repair (PNR). The right shoulder was used for experimental intervention, and the left served as a control. Four weeks after detaching the infraspinatus, the torn tendon was repaired. Saline, PDRN, and PN were applied to the repair sites. Histological evaluation was performed 3 and 6 weeks after repair and biomechanical analysis was performed at 6 weeks. RESULTS: Three weeks after repair, the PR and PNR groups had more CD168-stained cells than the SR group. The PR group showed a larger cross-sectional area (CSA) of muscle fibers than the SR and PNR groups. Six weeks after repair, the PR and PNR groups showed more adipose cells, less CD68-stained cells, and more parallel tendon collagen fibers than the SR group. The PR group had more CD 68-stained cells than the PNR group. The PR group showed a larger CSA than the SR group. The mean load-to-failure values of the PR and PNR groups were higher than that of the SR group, although these differences were not significant. CONCLUSION PDRN and PN may improve tendon healing and decrease fatty degeneration after cuff repair.