We designed a randomized clinical trial with control group, to investigate the effects of platelet rich plasma (PRP) on pain, stiffness, function and quality of life in patients with knee osteoarthritis. Patients were randomly divided in two groups. For both groups of participants, therapeutic exercise was prescribed. In the PRP group, two courses of leukocyte rich PRP (5.6 fold higher platelet concentration) with a 4-week interval was injected. For each participant, Western Ontario and McMaster University's Arthritis Index (WOMAC) and the SF-36 questionnaire (Farsi version) were filled at the baseline and 6 months after treatments. Thirty-one patients in the PRP group and 31 patients in the control group were studied. Mean changes of total WOMAC, physical component summery and mental component summery of Short Form-36 in PRP group showed better improvement than control group (P<0.05). This study showed that intra articular PRP knee injection combined with therapeutic exercise can be more effective in pain reduction and improvement of stiffness and quality of life, compared with therapeutic exercise alone.