BACKGROUND: It has been theorized that tibialis posterior tendon dysfunction (TPTD) is a degenerative process unrelated to inflammation. The purpose of this study was to determine if inflammatory cytokines, matrix metalloproteases (MMPs), and glutamate were elevated in diseased tibialis posterior tendons (TPTs). METHODS: Matched diseased TPT, TPT insertion, and flexor digitorum longus (FDL) samples were collected from 21 patients. The samples were individually incubated in media, which was analyzed for inflammatory cytokines, MMPs, and glutamate. Histology and statistical analyses were performed. RESULTS: Diseased TPT and TPT insertion were significantly elevated compared to transferred FDL in eight inflammatory markers (p < 0.005). Only the diseased TPT was significantly elevated compared to the transferred FDL tendons for glutamate (p < 0.01). Histologic grading correlated with inflammatory cytokine levels. CONCLUSION: Diseased TPT and TPT insertion demonstrated significantly elevated levels of inflammatory markers compared to the transferred tendons used as controls, suggesting a role for inflammation in the disease process. The amount of inflammation correlated with increased tendon degradation. LEVEL OF EVIDENCE: Level III.