Abstract: AIM To study the inhibitory effects of benzoisoselenothiazolidone sulfonamide derivatives on cyclooxygenase. METHODS 6-Keto-PGF_1α and PGE-2 were assayed by radioimmunoassay (RIA) method; mRNA expression of COX-1 and COX-2 were assayed by reverse transcription-ploymerase chain reaction (RT-PCR) method. RESULTS Compound A N-4-(4-methoxyphenyl-aminosulfonyl)-benzoisoselenothiazolidone and B N-4-(4-fluorophenyl aminosulfonyl)-benzoisoselenothiazolidone were two benzoisoselenothiazolidone sulfonamide derivatives, which can inhibit COX activity with IC₅₀ of 1.5×10^-8 mol·L^-1 and 5.0×10^-8 mol·L^-1 for COX-2, as well as IC₅₀ of 1.5×10^-5 mol·L^-1 and 2.8×10^-5 mol·L^-1 for COX-1. The ratio of IC_{50 COX-1}/IC_{50 COX-2} of compound A and B are 1 000 and 560, respectively. They both can inhibit COX-2 mRNA expression in cultured rat peritoneal macrophages stimulated with LPS (1μg·mL^-1), and have no effect on COX-1 mRNA expressions. CONCLUSION Compound A and B, two benzoisoselenothiazolidone sulfonamide derivatives, both are selective inhibitory agents of COX-2, and possess inhibitory effects on 5-lipoxygenase and cyclooxygenase.