This paper reports an innovative design of reel-to-reel hot embossing system for the production of plastic microlens array films. The novel system mainly consists of a reel-to-reel mechanism with tension rollers, a gas-assisted hot embossing module and a vacuum-assisted de-molding unit. During this new process operation, a thin steel mold with large-area micro-circular hole array pattern was fixed on the bottom hot plate of this system. The part of plastic film roll was placed on the mold by tension rollers. Under the proper processing conditions, the softened polymer will just partially fill the micro-circular holes of the mold and, due to surface tension, form a convex lens surface. After a proper cooling process, the plastic film with a large-area microlens array pattern was de-molded from the mold by reverse pressure activated through the vacuum system. In this way, a roll of plastic film with a large-area microlens array can be successfully fabricated. In addition, the sag height, curvature, and focal length of the fabricated microlens arrays could be changed and controlled. The embossing by gas pressure is uniform and the de-molding by a vacuum system is running smooth. This technique shows great potential for mass production of plastic optical films with various large-area microlens arrays.