To correlate the changes in periarticular tissue levels of pro-inflammatory cytokines and endothelin-1 (ET-1) to local pathophysiology in rats with antigen-induced arthritis (AIA). The periarticular soft tissue was excised from sixty-six rats at different stages of AIA. The samples were homogenized and the levels of immune like (LI) reactivities were determined. The levels in the arthritic joints were compared to those in non-arthritic tissue. Statistical significance was determined by ANOVA followed by Fisher PLSD. Compatible with a role in an early alarm reaction some mediators (tumor necrosis factor alpha-LI, interleukin-2-LI and interferon-gamma-LI) were elevated prior to the vascular inflammatory activity. The curve for ET-1-LI closely followed the intensity of the inflammation whereas these parameters preceeded the elevation of interleukin-1beta-LI. Transient waves of different mediators appear during the course of the arthritis. This indicates the presence of active downregulatory mechanisms. Here the model could differ from human rheumatoid arthritis.