6-Bromo-4-chloro-1-hydrazinobenzothieno[2,3-d] pyridazine (1) was selected as the starting material for the synthesis of some novel fused benzothienotriazolopyridazine derivatives 2–16. Thus, compound 1 was reacted with carbon disulfide, ethyl orthoformate, acetic anhydride, or 2-methoxybenzaldehyde followed by cyclization with bromine, to give the corresponding benzothienotriazolopyridazines 2–6. Nucleophilic substitution of the 6-chloro with piperidine, N-methyl piperazine, hydrazine hydrate, or potassium hydroxide afforded 6-substituted benzothieno[3,2-d][1,2,4]triazolo[4,3-b] pyridazines 7–16. The structures of the synthesized compounds were elucidated by elemental analysis and spectral data. All the newly synthesized compounds were subjected to evaluation for their antiinflammatory activity against carrageenaninduced paw edema at a dose of 10 mg/kg using indomethacin as the reference standard. Compounds 11 and 13 (6-hydrazinyl derivatives) significantly reduced the edema to 52.8 and 78.7%, respectively, as compared with indomethacin (50.5%).