Background: Topical application of herbs is one of the recommended treatment modalities for Osteoarthritis (OA) in Ayurveda (Indian system of medicine). The current study intended to evaluate the anti-inflammatory effect of a polyherbal powder used as Upanaha (poultice) for OA by in vitro and in vivo techniques. Materials and Methods: The polyherbal formulation Upanaha Choornam (UC) was sourced from Vaidyaratnam Oushadhasala (P) Ltd., Thrissur, India. Changes in the secretion of TNF-α and NO and expression of Cox-2 genes were evaluated by semi quantitative PCR activity to establish anti-inflammatory action in vitro. Macrophages and connective tissue of mice were used as media for the former two experiments and only macrophages for the latter. In vivo anti–inflammatory activity was evaluated by TPA induced ear oedema in Swiss Albino mice (n=24), divided into 4 groups as Group I - saline treatment, Group II - Indomethacin treatment, and Groups III and IV treated with 30% and 60% of UC respectively. Results: In the in vitro study, UC at 1000 µg/ml and 500 µg/ml upregulated the COX-2 level by 0.08 and 0.03 folds respectively as compared to control. Release of TNF-α, and NO in LPS-induced RAW cells were significantly inhibited in a dose dependent manner. The TPA induced ear oedema significantly reduced in Groups III and IV (F=1250, p less than 0.001) Conclusion: The current study demonstrates the safety and anti-inflammatory activity of a polyherbal formulation Upanaha Choornam as a topical application. This indicates the potential of select herbs in managing degenerative conditions like OA.