Background: Tea polyphenols (TPs) attenuate obesity related liver inflammation; however, the anti-obesity effects and anti-inflammatory mechanisms are not clearly understood. This study aimed to determine whether the anti-obesity and anti-inflammatory TPs mechanisms associated with cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression levels, and obesity-related gene response in dogs. Results: Dogs fed TPs displayed significantly decreased (p < 0.01) mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) compared to dogs that consumed high-fat diet (HFD) alone. TPs significantly (p < 0.01) inhibited COX-2 and iNOS expression level, and decreased liver fat content and degeneration. Conclusion: These results suggested that TPs act as a therapeutic agent for obesity, liver inflammation, and fat degeneration via COX-2 and iNOS inhibition, with TNF-α, IL-1β, and IL-6 involvement.