Abstract: Aim ：To study the synthesis and anti-inflammatory activity of p-(sulfamyl)benzylidene-linked heterocyclic ketone derivatives. Methods ：A series of p-(sulfamyl)benzylidene-linked heterocyclic ketone derivatives were synthesized.Anti-inflammatory activity was evaluated against xylene-induced ear oedema in mice and against carrageenan-induced paw oedema in rats.Gastrointestinal side effects in the rats were also examined after continuous introgastric administration of these compounds once daily for 7 days. Results ：Twelve compounds(LHZ-101-LHZ-112)were synthesized and their structures were confirmed by IR，¹H NMR，MS and elemental analysis.LHZ-105，LHZ-106 and LHZ-111 exhibited marked anti-inflammatory activity in xylene-induced mice ear swelling model.LHZ-106 and LHZ-111 showed significant anti-inflammatory activity in carrageenan-induced rat paw edema model.LHZ-105，LHZ-106 and LHZ-111 had less gastrointestinal side effects than diclofenac sodium and CI-1004. Conclusion ：These results suggest that some of these compounds have the potential for anti-inflammatory activity with few gastrointestinal side effects.