Background: Avocado/soybean unsaponifiables such as Arthrocen have been reported to reduce cartilage catabolism and chondrocytic synthesis of inflammatory mediators associated with osteoarthritis (OA). While there is some clinical evidence that avocado/soybean unsaponifiables can reduce OA pain, no preclinical studies have corroborated this observation. The present study determined whether addition of an avocado/soybean unsaponifiable (Arthrocen) to the drinking water of OA rats reduced direct and referred joint pain. Methods: OA was induced in male Wistar rats by intra-articular injection of sodium monoiodoacetate (MIA: 0.3mg) and animals were allowed to recover for 14 days. Arthrocen was added to the drinking water which was available to animals ad libitum. On day 30, joint pain was assessed by dynamic incapacitance while referred pain was determined by von Frey hair algesiometry. Results: The joint damage induced by MIA injection was severe and was consistent with end-stage OA. Arthrocen consumption (approximately 35 mg/day) attenuated the joint oedema associated with MIA injection. Hindlimb weight bearing also significantly improved in Arthrocen-treated rats (P<0.05); however, von Frey hair mechanosensitivity was unaffected by this treatment. Conclusions: These data indicate that Arthrocen has the potential to reduce joint inflammation and pain associated with end-stage OA.