In this study, lubricin, a protein involved in the lubrication of joints, was discovered to bind to and activate toll-like receptors (TLR). Since TLRs are a major component of the innate immune system, this suggests that lubricin may also play a role in the regulation of the inflammatory response. We attempted to elucidate whether lubricin has a pro- or anti-inflammatory role in the joint following TLR binding. To determine if lubricin-TLR interaction could be playing a role in Osteoarthritis (OA), we examined the cytokine secretions of OA fibroblasts treated with lubricin and demonstrated a potentially anti-inflammatory effect. Furthermore, in vivo studies demonstrated lubricin’s ability to mitigate pain, joint damage, and inflammation following an injury in a rat OA model. The experiments presented in this thesis suggest that lubricin could have anti-inflammatory effects when binding to TLRs at the cellular and tissue level.