Summary: In the present study, a comparison was made among the efficiencies of four common extraction methods used for extraction of Quercitannin content of oak leaves. These extraction methods are Maceration, Soxhlet, and microfluidic extraction without and with ultrasonic wave irradiation. Several solvents including methanol, ethanol, hexane, and water were used during the experiments. Amount of Quercitannin obtained through a microchannel in the ultrasonic bath was higher than those of Soxhlet, Maceration, and plain ultrasonic bath extractions. This study is also aimed to study the extraction factors including frequency, temperature, and power ultrasonic in a microchannel with ultrasonic wave irradiation. Moreover, the optimal possible hybrid of these factors over response surface methodology was obtained. The optimum condition was the ultrasonic treatment at frequency = 80 kHz, temperature = 75ºC and power = 40w. Under these conditions, the yield using ultrasonic bath with microchannel was increased 17.57% and 32.68% compared with the plain microchannel and simple ultrasonic bath, respectively. The proposed continuous flow system uses less amount of solvent, producing less amount of waste. Besides, this system needs a smaller space compared with other conventional methods. Therefore, the use of microchannels as a way of the continuous method provides an environmentally friendly and high efficiency method in comparison with conventional methods.