With the development of microscopic imaging technology, the autofocus method has been adopted more widely. An innovative autofocus solution is presented based on liquid lens used in microscope imaging system through optical simulation and experiment. Firstly, two commercialized liquid lens are discussed on its principle and application, and Optotune lens was chosen as the autofocus device for microscopic imaging system. Secondly, the liquid lens is integrated into the system design and the optical performances are simulated. Finally, the experiment is carried out in order to evaluate the functionality and performance of the integrated system. Experiment results show that the depth of field of the system can be extended to 1mm while maintain good image quality. The autofocus technology based on liquid lens has the advantage of compact design, fast focusing, and low cost without compromising its optical performance.JIANG Decai. Design and Development of Auto-Controlled stage for bio-microsystem [D]. Jinan：Shandong Univeristy，2007： 10-19.