A new series of trisubstituted pyrazoline bearing benzenesulfonamide moiety 6a,b–10a,b were designed, synthesised and evaluated for their anti-inflammatory in vitro. Before starting the synthesis, docking study has been used to insert compounds within the COX-2 structure active site using celecoxib drug as a reference. Final compounds 6a,b–10a,b were synthesised by condensing chalcones bearing pyridine moiety 1a,b–5a,b with 4-hydrazinyl benzenesulfonamide hydrochloride. In vitro, their anti-inflammatory activity was assessed using egg-white paw edema method, they showed moderate to strong inhibitory activity. Notably, Compounds 6a (29.78%), 7a (28.43%), 9a (27.92%) and 10a (27.92%) exhibited significant percentage inhibition at 300 min and results are comparable with percentage inhibition drug celecoxib (22.67%) and this result is highly agreement with docking scoring study.