Injury‐related, post‐traumatic osteoarthritis (PTOA) is a disease of the joints caused by an imbalance between extracellular matrix destruction and production. We have developed an innovative disease modifying therapeutic technology to treat PTOA. Extracellular matrix protection factor (ECPF‐1) is a novel, safe and effective intra‐articular injection that reduces the pain and damage caused by OA. Utilizing the peptide as an early intervention therapeutic, we have assessed its effects on the progression of PTOA. Peptide or control saline was injected into the injured knee joint for four consecutive weeks. Endpoint assessment of: toxicity, measured by CBC and serum chemistry; joint space narrowing, measured by Xray; joint functionality, measured by stride test; and tissue pathology, measured by micro computed tomography and histology were completed. Intra‐articular injections of ECPF‐1 in a rat model of PTOA demonstrated no cellular toxicity, normal serum chemistry following 4 weekly injections, diminished tissue destruction and increased animal mobility. All data indicates that ECPF‐1 is non‐toxic and diminishes the pathology associated with OA. Grant Funding Source: Supported by intramural funds