A series of mannich bases of 2,5-disubstituted indoles have been synthesized by reaction of 2,5-disubstituted indoles with secondary amine and formaldehyde in acetic acid. The title 2-substituted indole were synthesized using a Fischer-indole synthesis gave substituted acetophenone phenylhydrazone and Cyclization of the hydrazone by polyphosphoric acid at 120°C afforded the 2-substituted indole. Nitration of 2-substituted indole was carried out in presence of equal amount of concentrated sulphuric acid and concentrated nitric acid. Most of the test compounds showed appreciable inhibition of the oedema size in comparison with diclofenac sodium. The compound MB11 had shown pronounced activity after 4th hour interval, almost equipotent with the standard drug diclofenac sodium. The compound MB4, MB5, MB10, MB15 and MB16 showed excellent protection against inflammation with 68%, 70%, 76%, 74% and 72% inhibition, respectively. The structures were confirmed by FTIR, 1H NMR.