Eighty patients with knee osteoarthritis were randomized to receive either warm needle acupuncture with Xitong Waixi lotion (n=40) or Xitong Waixi lotion alone (n=40). The primary outcome of this trial was to determine the levels of interleukin-1 (IL-1), tumor necrosis factor-a (TNF-a), and matrix metalloproteinase-3 (MMP-3) after treatment. Pain and knee function were also assessed using the Visual Analog Scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and Hospital for Special Surgery (HSS) scales, respectively. Significant differences were apparent in IL-1, TNF-a, and MMP-3 levels after treatment with better levels in the combination group. VAS, WOMAC, and HSS scores were also significantly better after treatment in the combination group.