Abstract： Objective： To observe the clinical effect of ultrasound- guided medication with prescription for joint pain combined with acupuncture for post-traumatic knee osteoarthritis and its effects on levels of matrix metalloproteinase-1 (MMP-1)，matrix metalloproteinase- 3(MMP-3) and transforming growth factor- β1(TGF-β1) in synovial fluid. Methods：A total of 84 cases of patients with post- traumatic knee osteoarthritis were selected and divided into the control group，the ultrasound group， the acupuncture group and the experiment group， with 21 cases in each group. The control group was given routine treatments，based on which the acupuncture group was treated with acupuncture，the ultrasound group was treated with ultrasound- guided medication with prescription for joint pain， and the experiment group was treated with ultrasound- guided medication with prescription for joint pain combined with acupuncture. The four groups were treated for four weeks. Pain degrees， joint function and levels of MMP- 1， MMP- 3 and TGF- β1 in synovial fluid before and after treatment among the four groups were compared. Results： After two and four weeks of treatment， VAS scores in the experiment group and the acupuncture group were lower than that in the control group(P＜0.05)， and VAS score in the experiment group was lower than that in the ultrasound group(P＜0.05)；there was no significant difference being found in the comparison of VAS scores between the experiment group and the acupuncture group(P＞0.05). After two-week treatment， Lequesne scores in the experiment group and the ultrasound group were lower than that in the control group(P＜0.05)，and Lequesne score in the experiment group was lower than that in the acupuncture group(P＜0.05)； there was no significant difference being found in the comparison of Lequesne scores between the experiment group and the ultrasound group(P＞ 0.05). After four- week treatment， Lequesne scores in the experiment group， the acupuncture group and the ultrasound group were lower than that in the control group(P＜0.05)，and Lequesne score in the experiment group was lower than that in the acupuncture group(P＜0.05)； there was no significant difference being found in the comparison of Lequesne scores between the experiment group and the ultrasound group(P＞0.05). After two-week treatment，levels of TGF-β1 and MMP- 3 in synovial fluid in the experiment group and the ultrasound group were lower than that in the control group(P＜0.05)，and MMP- 1 levels in synovial fluid in the experiment group，the acupuncture group and the ultrasound group were lower than those in the control group(P＜0.05)；levels of TGF-β1 and MMP-3 in synovial fluid in the experiment group were lower than those in the acupuncture group and the ultrasound group(P＜0.05)，levels of MMP-3 in synovial fluid in the experiment group was lower than that in the acupuncture group(P＜0.05)；there was no significant difference being found in the comparison of MMP- 3 levels between the experiment group and the ultrasound group(P＞0.05). After four- week treatment， levels of TGF- β1， MMP-1 and MMP-3 in synovial fluid in the experiment group，the acupuncture group and the ultrasound group were lower than those in the control group(P＜0.05)， levels of TGF- β1， MMP- 1 and MMP- 3 in synovial fluid in the experiment group were lower than those in the acupuncture group and the ultrasound group(P＜0.05). Conclusion： Ultrasound- guided medication with prescription for joint pain combined with acupuncture for post- traumatic knee osteoarthritis can significantly relieve pain，promote the recovery of joint function，and reduce levels of MMP-1，MMP-3 and TGF-β1 in synovial fluid.