The ester derivatives of indomethacin were prepared by condensing indomethacin with an equimolar quantity of an appropriate alcoholic compound in anhydrous dichloromethane in the presence of DCC and DMAP. Spectral studies comprising of IR, 1 H NMR, mass, and microanalysis were performed in order to confirm their structures. In vivo anti-inflammatory studies were carried out using carrageenan rat paw edema method and in vivo ulcerogenic studies by ulcer index method for the panel of synthesized compounds. Out of eleven compounds, the compound IIc displayed moderate anti-inflammatory activity with no observable ulcerogenic effect when compared to indomethacin. Furthermore, compound IIc, indomethacin and celecoxib were tested at a concentration of 20 lM against COX-1 and COX-2 enzymes by colorimetric COX inhibitor screening assay. Compound IIc was found to be active against COX-2 and COX-1 enzymes exhibiting 62.0 and 12.9% inhibition, respectively.