Two natural Biopol polyesters, containing 8% (D400G) and 12% (D600G) of hydroxyvalerate component, and a synthetic polyester based on 1,4 cyclohexanediol [Poly(cyclohexyl-sebacate)--PCS] were studied to investigate their in vitro and in vivo behavior for application in musculoskeletal tissue repair. The polyesters were placed in direct contact with L929 fibroblasts and cell proliferation (WST-1), cytotoxic effect (LDH), synthetic activity (total proteins) and cytokine production (IL-1beta, IL-6, TNFalpha) were assessed after an incubation period of 72 hours and 7 days. Then, 12 Sprague-Dawley rats underwent dorsal subcutaneous implants of tested polyesters under general anesthesia. After 1 and 4 weeks from surgery, the animals were pharmacologically euthanized and the implants retrieved with surrounding tissue for histologic and histomorphometric investigations. In vitro results showed that D600G behaved a little worse in comparison to other tested polyesters in terms of cell proliferation and TNFa at 7 days. PCS presented the lowest total protein value at 7 days. In vivo results indicated that PCS implants produced a higher (p < 0.01) extent of inflammatory tissue in comparison to D600G at 1 week and to D400G at 4 weeks, and the lowest vascular densities at both experimental times. D400G seems to be the most suitable material for biomedical application when tested in fibroblast cultures and in the subcutaneous tissue of rats.