Artemisinin is a kind of natural antimalarial drug exhibiting low toxicity and a very fast action against malaria. Solvent extraction is the most widely used method to separate artemisinin from the Chinese medicinal herb Artemisia annua L. In this study, a series of monoether-based solvents were investigated to extract artemisinin, and propylene glycol methyl ether (PGME) was found to be the most appropriate one for this extraction. Ultrasonic irradiation was demonstrated to be able to assist artemisinin extraction. Influence of extraction conditions, including liquid/solid ratio, extraction temperature, ultrasonic time, and ultrasonic power, on the extraction efficiency were discussed by single-factor experiments, and the main influencing factors were optimized by response surface methods. The extraction mechanism was explored using spectroscopic characterizations, and kinetics of this process was also studied. Results indicated that ultrasonic assisted extraction using PGME had faster extraction rate than conventional solvents, and ultrasonic could significantly enhance mass transfer. Compared with conventional extraction, the process developed here exhibited a higher efficiency (13.79 mg g(-1) vs. 13.29 mg g(-1)) and shorter extraction time (decreased from 8 h to 0.5 h) at a relatively low temperature. In addition, PGME had low toxicity and volatility, making the extraction process more safe and reliable. Therefore, this proposed method demonstrated that PGME-based ultrasonic assisted extraction is a rapid, efficient, simple and safe technique for natural product extraction.