Rotator cuff tear is the major cause of morbidity which affects over 40% of patients aged 60 years and older. Surgical repair is often unsuccessful and has high complications. Tissue engineering therapies, such as applying Mesenchymal stem cells (MSCs) secretomes, have shown beneficial effects on tendon repair. This study aims to assess the effect of secretome application on rotator cuff tendon tears by examining changes in transforming growth factor beta (TGF-β), Scleraxis, and Collagen type III levels. A total of 20 post-injured supraspinatus tendon New Zealand white rabbits were divided into 2 groups: injected with of frozen-dried tenogenic secretome (treatment group) and no treatment (control group). Histologic evaluation on the repaired site was conducted on the second and the fourth weeks; analysing immunohistochemistry (IHC), TGF-β, Scleraxis, collagen type III levels, modified tendon maturing score, blood vessel, fibroblast, and fibrotic tissue. Immunoreactive Score (IRS) result for TGF-β, Scleraxis, and collagen type III on treatment group were moderate. Meanwhile, IRS result for control group was a mix of mild and moderate. Compared to the control group, a significant difference was found (p<0.05). Histologically, Modified Tendon Maturing Score, amount of blood vessel, and fibroblast were found to be significantly higher (p<0,05) in treatment group. Meanwhile, fibrotic tissues were significantly lower (p<0,05). Secretomes promote the healing of specific tissues such as tendons in vitro and in vivo. TGF-β is crucial for collagen synthesis, while scleraxis facilitates tendon-bone attachment. Collagen type III initiates tendon repair, requiring increased blood vessel and fibroblast growth and lower fibrotic tissue.