The purpose of this research is to synthesize better anti-inflammatory compounds derived from 5-mercapto-3-(40 -pyridyl)-4H-1,2,4-triazol-4-yl-thiosemicarbazide (5). 2-Substituted-N-[3-(pyridin-4-yl)-5-sulfanyl-4H-1,2,4 triazol-4-yl]hydrazine carbothioamide derivatives (6a–j)/ (7a–e) are synthesized by the condensation of 5 with variously substituted aromatic aldehydes/1H-indole-2,3-diones, respectively, under conventional and microwave irradiation methods. The microwave method is found to be superior with higher chemical yields, tremendous reduction in time, and is environmentally benign as compared to conventional heating method. The chemical structures of the newly synthesized compounds (6/7) have been confirmed by IR, 1 H NMR, and 13C NMR spectra and have been evaluated for anti-inflammatory activity by carrageenan-induced acute paw edema method in rats.