The purpose of the present study was to evaluate the effect of local application of Autologous Conditioned Plasma (ACP) on the treatment of full-thickness cartilage injuries of the knee. The hypothesis of the study was that ACP can enhance healing response of injured cartilage. A full-thickness chondral lesion on the weight-bearing area of the medial femoral condyle was performed in 30 sheep. Animals were divided into 2 groups, according to postoperative treatment: in group 1, weekly injections of ACP for five times were performed; in group 2, lesions were left untreated. Animals were sacrificed at 3, 6 and 12 months after treatment. A histological evaluation was performed according to a modified O'Driscoll histological score. Comparison between groups for each time interval was performed with the Student's t-test. Significance was set at P<0.05. A post-hoc power analysis was performed according to the hypothesis of the study. Histological evaluation at 3 and 6 months showed that group 1 had significantly greater total score than group 2. At 12 months, no significant difference was observed between groups. In conclusion, local injections of ACP for treatment of full-thickness cartilage injuries did not produce hyaline cartilage. However, it promoted reparative response of the cartilage defect until 6 months after treatment.