Inflammation is a reaction of a living vascularised tissue to an injury. Conventional or synthetic drugs used in the treatment of inflammatory diseases are inadequate, it sometimes have serious side effects. So, number of herbal medicines is recommended for the treatment of inflammation that has no side effects. Pongamia pinnata, Pierre (Family- Fabaceae) commonly known as karanja. The seed and seed oil of the plant have been reported to be effective in various inflammatory and infectious diseases such as leucoderma, leprosy, lumbago, muscular and articular rheumatism, cutaneous affection including herpes and scabies etc. in folk medicine and Ayurveda, a traditional system of healing . Anti-inflammatory activities of this plant for various parts have been reported in various models. This study examined the anti-inflammatory potential of a methanolic leaves extract of Pongamia pinnata and reference drug Declofenac sodium, invitro using heat-induced protein denaturation technique. The concentrations of the leave extract used were 50-250μg/ml. While diclofenac sodium were 50, 100, 150, 200 and 250μg/ml. Both the Diclofenac sodium and extract showed the IC50 values 18.36 and 82.24µg/ml respectively. It is concluded that the methanolic leaves extract of Pongamia pinnata possess marked in vitro anti-inflammatory activity which is mediated possibly by flavonoids, tannins and alkaloids. This is a novel finding. Further the results scientifically justify the use of leaves of Pongamia pinnata in India traditional medicine to treat inflammation. Keywords: Inflammation, Pongamia pinnata, Fabaceae, heat-induced protein denaturation technique