An efficient one-pot method is used to prepare a series of N-aryl substituted piperazine hydrochloride from substituted aniline and N,N'-bis(2-chloroethyl)amine hydrochloride in 2-(2-methyloxyethoxy)ethanol under microwave irradiation. The reactions were completed in 3～4 min with 36.9%～75.4% yields. It is confirmed from the experimental results that substituents on the benzene rings of the substituted aniline exerted consistent influences in the ongoing N-aryl piperazination with that of plausible prediction. Compared with conventional heating method, the method of microwave irradiation possesses advantages including short time, hige yield, easy working out and environmental benignity. Their molecular structures were characterized by IR, 1H NMR and MS spectroscopy.