Abstract: This research was done to study the protein expression profile of synovial cells of knee using proteome analysis during the development of experimental Post-Traumatic Arthritis (PTA) in swine. PTA was induced by transection of the Anterior Cruciate Ligament (ACL) of left knee in three piglets. Articular cartilage and synovial tissues were obtained after 0, 2, 5 and 8 weeks for histopathologic examination. After sacrificing the piglets at 8 weeks, synovial tissues were collected for 2-dimensional electrophoresis and mass spectrometric analysis. Histopathologic examination at 8 weeks showed overt chronic inflammation indicating the development of ETA. Through proteome analyses more than 1,500 protein spots were identified in which 7 differentially expressed protein spots were observed in ACL-transacted synovial tissue. Five proteins were down-regulated (cytoskeletal β actin, cofilin-1, destrin, Rho GDP dissociation inhibitor α and an unnamed protein product) and two proteins were up-regulated (α-B crystalline and Smooth Muscle Protein (SMP) 22α). These results showed that proteins that are related to cellular organization and signal transduction are down-regulated and those that are related to cell rescue, defense and stress are up-regulated. Therefore, the proteome analysis of synovial tissue provided us new candidate molecules which may be useful to understand the pathogenesis for diagnostic and therapeutic studies of Post Traumatic Arthritis (PTA).