Piper betle L. also known as ‘Paan’ in India, is an important species of the Piperaceae family. The betel leaves are mainly used as a mouth freshener and have long been in use in the Indian indigenous system of medicine for the relief of pain. The present study was conducted to determine the In vitro anti-inflammatory activity of Piper betle L. leaf extracts. Ethanolic and aqueous extracts were prepared from dried betel leaves. In vitro anti-inflammatory activity of these extracts was investigated by inhibition of protein denaturation assay and results were compared with standard drug Diclofenac sodium. Both extracts exhibited concentration-dependent inhibition of protein denaturation. The IC50 value of both extracts was calculated and compared with standard drug.