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Objective To investigate whether the cartilage regenerative effects of intra-aricular platelet-rich plasma (PRP) are different, according to the severity of osteoarthritis (OA), in a collagenase-induced knee OA rabbit model.Method New Zealand white rabbits (N=21) were randomly divided into three groups. Three different doses (0.25 mg, group 1; 0.5 mg, group 2; and 1.0 mg, group 3) of collagenase were injected twice into both knees of each group under an ultrasound guidance. The mean platelet concentration of the PRP fraction was 2,664±970×103/μl and was enriched 8.2-times, compared with the whole blood. PRP (0.3 ml) was injected into the left knee and saline (0.3 ml) into the right knee at 4 weeks, and macroscopic and histological scores of both injected knees were evaluated at 9 weeks after the first collagenase injection.Results Macroscopic and histological scores of group 3 were significantly higher than those of group 1 and 2 (p<0.05). Macroscopic and histological scores of the PRP-injected knees were significantly lower than those of the saline-injected knees, in all groups (p<0.05). Differences of gross morphologic and histologic scores between sa-line- and PRP-injected knees in group 3 were significantly higher than those in group 1 and 2 (p<0.05).Conclusion Intra-articular PRP injection influences cartilage regeneration in all severities of rabbit knee OA, and the cartilage regenerative power of PRP injection in moderate knee OA was greater than that in mild or very mild OA. A large preclinical trial is needed to establish the validity of our study.