Insulin-like growth factor I (IGF-1) is the most important known growth factor for cartilage repair in horses. It promotes mitosis of chondrocytes, collagen II expression, and extra cellular matrix production. Osteoarthritis (OA) is the most common musculoskeletal condition that causes lameness and poor performance in sport horses. A total of 11 lame horses were clinically and radiographically evaluated, and all were confirmed to suffer a front metacarpophalangeal lameness by a positive flexion test, a low-4-point nerve block and an intraarticular block. Total protein, IGF-1, IL-6 and TNFa were determined by ELISA, demonstrating changes and different correlations between clinical condition, radiographic changes and degree of inflammation. All horses with joint associated pain and therefore associated lameness, demonstrated a significant increase of total protein (P<0.0001) and IGF-1 concentration (P<0.05). Concentrations of IL-6 and TNFa between controls and lame horses demonstrated significant differences (P<0.01 and P<0.001 respectively). Horses with less radiographic changes, demonstrated the highest IGF-1 expression in synovial fluid, and horses with more chronic OA conditions had very similar IGF-1 expression levels than control joints. In all lame joints, it was identified by Western blot a lighter isoform of IGF-1 (~7.5 kDa) which was inflammation related and it is the molecular weight of the mature peptide, and all control joints expressed a heavier isoform (~12 kDa). This finding could lead to new research for sequencing and targeting the isoform which is not expressed during an inflammatory process within a joint, and to have a better understanding of its role in the horse’s joint.