Several fatty chain palmitylthiadiazole derivatives have been synthesized by reaction of palmitic acid with thiosemicarbazide in presence of phosphorous oxytrichlorideto afford the corresponding 5-pentadecanyl-amino thiadiazole which in turn has been reacted via its nucleophilic amino group with different reagentssuch as acid chlorides, acid anhydrides, aldehydes and isocyanates to give the corresponding 5-pentadecanyl-2-amino-1,3,4- thiadiazole derivatives in an excellent yield.The antimicrobial study of all products has been screened and showed that most of thiadiazolecompounds exhibited high to moderate inhibitory effect particularly the acetamidothiadiazoloe2which showed the highest effect against all employed microorganisms. Structure of all products wascharacterised by IR, 1H-NMR, Mass spectra and elemental analyses.