The cranial cruciate ligament rupture (CrCLR) is characterized by chronic inflammation and osteoarthritis (OA) of the stifle joint and extracellular matrix (ECM) degeneration of the ligament itself in dogs. Generally, OA may arise from chronic low-grade systemic inflammation. We assessed the possible relationship of inflammatory markers in the peripheral blood (PB) and synovial fluid (SF) of affected stifle joints in comparison to a control. Moreover, no study has shown the possible association between PB and SF levels of inflammatory markers in CrCLR stifles of dogs in veterinary medicine yet. We also evaluated components of ECM of CrCLR and finally compared the tibial plateau angle (TPA) and the anatomical-mechanical angle (AMA) between groups. Samples from PB and SF were examined for mRNA expression of interleukins, TNF-α and INF-γ. ECM components—collagen 1A1 and 3A1 and elastin—were examined for mRNA expression from SF. The level of relative expression for IL-1β, IL-8 and IFN-γ was significantly increased in both PB and SF in CrCLR stifles as compared with the control. Collagens were also significantly increased in CrCLR stifles. TPA was not significantly different; however, the AMA angle significantly increased in the CrCLR group. Our results suggest a possible relationship between PB and SF levels of inflammatory markers in CrCLR stifles of dogs.