Some unnatural chalcones (1a-q) and flavones (2a-d) have been synthesized and evaluated for their antiinflammatory activity using carrageenan-induced rat paw edema assay. The flavone 2c (6-Chloro-7-methyl-3', 4'- dimethoxyflavone) had higher anti-inflammatory activity and superior gastrointestinal safety profiles than the reference drug celecoxib. Compound 2c showed almost two times better selective inhibitory activity towards COX-2 enzyme than celecoxib. 2'-Hydroxychalcones (1a-h) showed moderate to strong anti-inflammatory activity (38.6-82.4 % at 3h and 52.4-80.2 % at 5h). Among 2'-methoxychalcones (1i-q) 1k and 1q exhibited maximum activity 82.6% (at 3h) and 84.3% (at 5h) respectively.