A technique is developed for microscope autofocusing, which is called the eccentric light beam approach with high resolution, wide focusing range, and compact construction. The principle is described. The theoretical formula of the eccentric light beam approach deduced can be applied not only to an object lens whose objective plane is just at the focal plane, but also to an object lens whose objective plane is not at the focal plane. The experimental setup uses a semiconductor laser device as the light source. The laser beam that enters into the microscope is eccentric with the main light axis. A defocused signal is acquired by a symmetrical silicon photocell for the change of the reflected light position caused by differential amplification and processed by a microprocessor. Then the electric signal is power-amplified and drives a dc motor, which moves a fine working platform to an automatic focus of the microscope. The result of the experiments shows a ±0.1-?m precision of autofocusing for a range of ±500-?m defocusing. The system has high reliability and can meet the requirements of various accurate micro measurement systems.