Objective: comparing the efficacy of Pistacia atlantica oleoresin and placebo in the treatment of knee osteoarthritis patients. Study design: randomized, double-blind, placebo-controlled, two group parallel design, single-center, phase 2 of clinical trial. Study population: patients with knee osteoarthritis. Sample size: 100 patients. Inclusion criteria: male or female patients with 1 or 2 knees osteoarthritis according to the American College of Rheumatology criteria after physical examination and knee joint radiography, age of 40 to 85 years, flare of the disease after oral non-steroidal anti-inflammatory drug or acetaminophen discontinuation which have been used at least 3 days a week during the past month (flare means increase of at least 2 scores in the total pain subscale score in the beginning of the study), Western Ontario and McMaster Universities (WOMAC) pain subscale index at least 9 out of 20 in the beginning of the study. Exclusion criteria: secondary osteoarthritis (due to a definite disease); arthroscopy; surgery; knee joint injection during the past 6 months; history of knee replacement surgery; any serious systemic disease (such as concomitant infections, cardiovascular, hepatic and renal diseases); any other chronic inflammatory disease; intake of any other supplement except multivitamin; intake of non-steroidal anti-inflammatory drugs; intake of any steroidal drug, skeletal muscle relaxing drug, anti-depressant drugs, glucosamine, chondroitin, tramadol and topical analgesic drugs like capsaicin and generally any analgesic drug; any history of alcohol, drug and narcotics abuse; skin disease at the site of topical use of the oleoresin or placebo (knee); having fibromyalgia and other debilitating diseases affecting the knee; pregnant women; women planning pregnancy; lactating women. Interventions: Pistacia atlantica oleoresin skin ointment is administered to a group of about 50 patients every 8 hours on the knee for 1 month and placebo skin ointment is administered to another parallel group of about 50 patients every 8 hours on the knee for 1 month. Before intervention and 1 month after intervention, the primary and secondary outcome variables are evaluated. Primary outcome variables: extent of arthritis, extent of joint pain, extent of joint stiffness, extent of physical function. Secondary outcome variable: dose of acetaminophen.