A major problem with current animal models of pain is their lack of face validity and their vulnerability for false positive results. The present study evaluated the efficacy of the open field locomotor system, as an objective measure of pain-related behavior and analgesic efficacy in rodents. Adult, male, Sprague-Dawley rats (180-250 g) received intra-articular injections of monoiodoacetate (MIA; 1 mg) in the left knee joint. Mechanical allodynia using von Frey filaments, the weight bearing difference test and the open field locomotor activity test were performed every other day for 21 days, following the MIA injection. The antinociceptive effects of ibuprofen (50 and 100 mg/kg) on the MIA-induced nociception were also evaluated. MIA induced a significant reduction in the paw withdrawal threshold (PWT) and a significant alteration in the weight bearing difference compared with control rats. Similarly, MIA induced a significant reduction in locomotor activity, with respect to X total counts, that represent the overall locomotor activity in the horizontal plane, and X ambulatory counts, which in turn represent small scale movements, such as scratching and grooming, and lastly, Z total counts, that represent rearing or standing. Both doses of ibuprofen resulted in a significant reversal of the MIA-induced alterations in PWT and weight bearing difference. Furthermore, the two doses of ibuprofen resulted in a significant reversal of the MIA-induced reduction in locomotor activity, with respect to X ambulatory counts, but not Z total counts. Only the higher dose of ibuprofen reversed the X total counts. The open field locomotor system may successfully be used to predict the analgesic efficacy of compounds in models of joint inflammation and osteoarthritis.