Objective:To determine the changes in serum levels of inflammatory biomarkers and antioxidant levels among the knee osteoarthritis (OA) patients after treatment with Phyllanthus amarus (PP) by nanoparticle gel phonophoresis.Methods:This study was a randomized,double-blind,placebo-control,parallel-group,clinical trial involving 30 subjects with mild-to-moderate degree of knee OA.The patients were allocated to two groups using a computer-generated random numbers,and received conventional ultrasound therapy (control group,15 cases) and PP (treatment group,15 cases) once daily for 10 sessions.The pain was evaluated by visual analogue scale (VAS).Serum levels of tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbnent assay (ELISA).Nitric oxide (NO) was determined by modified Griess reagent.The antioxidant effects,including superoxide dismutase (SOD) and total antioxidant capacity (TAC),were also measured by ELISA assay.Results:The VAS score was significantly decreased in the treatment group compared with the control group after treatment (P＜0.01).The serum concentrations of TNF-α and NO were significantly reduced in the treatment group compared with the control group (P＜0.01) after treatment.However,the serum concentrations of SOD and TAC in the treatment group were significantly higher after treatment compared with the control group (P＜0.01).Conclusion:PP could alleviate knee pain and significantly reduce systemic antiinflammatory effects in knee OA patients.