Background: Biomarkers may reflect changes in cartilage metabolism and could be used in diagnosis and evaluation of treatment response in knee osteoarthritis. The aim of this study is to determine the effect of platelet rich plasma (PRP) injections on serum and urine biomarkers in patients with knee osteoarthritis (OA). Methods: The study included 26 patients who were diagnosed as grade III knee OA according to ACR criteria and Kellgren-Lawrence classification. One cc of PRP was obtained from 20 cc of venous blood after double centrifugations at 400 g for 10 minutes. The patients received 3 injections of PRP at 3-weeks intervals. Serum Procollagen II N-terminal propeptide (PIINP), osteocalcin (OC), cartilage oligomeric matrix protein (COMP) and urine collagen-II telopeptide (U-CTX-II) were examined in all patients before treatment and at 3 and 6 months. Clinical outcome was evaluated using Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire, SF-36 and visual analog scale (VAS) in all patients before injection and at 3 and 6 months follow-up visits. Results: There was no statistically significant difference in cartilage Type II collagen (CII) degradation markers (CTX-II, COMP) and biosynthesis marker of PIINP (P>0.05). Significant increase was determined in serum OC levels (P<0.05) which reflects CII biosynthesis. Statistically significant improvement in all WOMAC parameters (P<0.05) and subscores of SF-36 (P<0.05) was noted. Conclusion: We found significant clinical improvements in knee OA patients treated with PRP injections. Our results suggest that PRP injection does not affect cartilage breakdown but effects CII biosynthesis, which is reflected by increased OC levels. However further studies are needed.