Irreparable tendon ruptures constitute a grave clinical problem. Especially for large rotator cuff tears, there often is no primary causal therapy available. As a sad result, the development of a rotator cuff tear arthropathy is more often than not inevitable. Our study investigates the effects of scaffold based tendon regeneration with special focus on mesenchymal stem cells in a rat model. We used ‘native’ bone marrow stromal cells and cultivated mesenchymal stem cells from male rats that were implanted into female rats. As scaffolds polyglycol acid (PGA) and a collagen I were used. A full-thickness-defect of 2–3 mm in the middle third of the rats achilles tendon was created, which was then filled, with either cell-seeded or not cell-seeded scaffolds and, due to the low primary stability of the scaffolds, fixed with a 4-0 suture. After 12 weeks, a DNA PCR was conducted to verify the existence of male Y-chromosomes in the female regenerated tissue. We determined the maximum tensile load of the regenerated tissue and also did a histological evaluation. Macroscopically the regenerated tendons were much bigger in diameter, much firmer and also much less elastic than a normal tendon. In the ‘mesenchymal stem cells’ group the implanted cells could be clearly identified after 12 weeks by DNA PCR. The collagen I scaffold yielded better results in the biomechanical study than the PGA scaffold. No evidence of positive influence of the cells on the mechanical stability of the regenerated tissue was found. Collagen I and the use of BMSC histologically lead to increased ossification of the regenerated tissue. In the PGA scaffold group a significant inflammatory reaction was found. Both scaffold/cell combination seem to be unsuitable for tendon replacement. in-vitro studies on the influence of scaffold material on cell differentiation needs to be done.