Synovial inflammation contributes to osteoarthritis (OA). Timely and effective treatment of synovitis may result in disease modification. The study objective was to compare the effects of intra-articular treatment with triamcinolone (TA) to autologous conditioned serum (ACS) in an IL-1β induced synovitis model. The fetlock joints of six healthy, adult horses were randomly assigned to treatment with the following: PBS, IL-1β (100 ng), ACS, IL-1β+ACS, and IL-1β+TA. Lameness, joint swelling, heat, and effusion were scored and recorded for 72 hours after each treatment. Synovial fluid was collected at 0-, 8-, 24-, and 48-hours post-injection (PIH) for cytology, PGE2 and glycosaminoglycan measurement. ACS (at 24, 36, and 72 PIH) and TA( at 24 and 48 PIH) treatments reduced lameness compared to IL-1β. IL-1β+ACS produced the highest synovial total nucleated cell count (TNCC ) (40,625 ± 11.01 cells/µL; P=0.001) and TP (3.73 ± 0.63 g/dl) at all time points. At 8 PIH, IL-1β treatment increased PGE2 concentration (P < 0.001), while GAG concentration was higher at 24 and 48 PIH (P < 0.001) for the TA group compared to the other treatment groups. ACS improved lameness scores despite an increased TNCC, while TA treatment had a reduced TNCC compared to ACS, but GAG concentration in synovial fluid. Limitations of this study include production of a mild, self-limiting synovitis in a small sample size and limited measurement of synovial inflammatory cytokines. In conclusion, ACS could improve pain and aid resolution of inflammation in acute synovitis.