Background: Osteoarthritis is a leading cause of pain, disability, and socioeconomic cost worldwide and the knee is one of the most commonly affected joint. Objective: to evaluate clinical and functional therapeutic effect of ultrasound guided intraarticular or periarticular platelet rich plasma (PRP) injection in treatment of patients with primary knee osteoarthritis. Patients and Methods: eighty patients with primary knee osteoarthritis were divided into two groups: Group I: 50 knees, group II: 30 knees. Both groups were treated by PRP injection into the lateral recess of the knee group I or into painful periarticular structure that have previously been identified on ultrasound group II. Results: The VAS in group I (6.3±1.45) and II (6.57±1.30) significantly improved after injection (1.30±0.97 and 1.43±0.77; p<0.001). The range of movement (ROM) (flexion) significantly improved in both groups after injection. The WOMAC significantly improved in both groups after injection (p<0.001); (group I: 14.04±7.73 vs group II: 15.20±7.12). The KOOS score significantly improved in group I (41.93±11.05 to 75.43±7.70; p<0.001) and group II (39.83±12.46 to 76.08± 7.12; p<0.001) after injection. There was a significant improvement in the percentage of different parameters in mild and moderate knee osteoarthritis in both groups. Conclusion: Ultrasound guided single dose PRP injection is a safe and effective method for treating all grades of knee OA mainly mild to moderate also injection in periarticular pain generator structures reduce pain and improve knee function.