A series of Schiff’s bases i.e., N-(4-(benzylideneamino)-2-phenoxyphenyl)-4-methylbenzene-sulfonamide were synthesized from Nimesulide and studied for their in vivo anti-inflammatory activity. Hydrolysis of Nimesulide with sulphuric acid led to the formation 1 which on further reaction with benzene sulphonyl chloride yielded the title compounds 2. Compounds 2 reduced with tin in presence of con. HCl yielded compound 3 which further refluxed with different benzaldehyde in presence of ethanol for synthesis of Schiff’s bases of Nimesulide. All the synthesized derivatives were characterized with FTIR and NMR spectral analysis and evaluated for their anti-inflammatory activity in-vivo.