The preparation of microstructures with certain patterns on a large-area substrate, especially on a flexible substrate, is a critical step in the development or production of flexible electronics (or macroelectronics). In this article, a novel roller-reversal imprint (RRI) process for the generation of large-area microstructures is proposed. In contrast to other published roller-imprint processes (such as hot embossing and ultraviolet roller-imprint), in which the material to be patterned is firstly film coated on the substrate and then the mold roller is pressed to the film, the RRI process starts with coating of the ink (mostly various liquefied electronics materials, such as a semiconductor polymer) on a patterned mold roller and then transferring the patterned ink to the substrate. The RRI process can be used to prepare micropatterns of various ink materials on a flexible substrate. By properly controlling the ink filling the microcavities on the mold roller and ink transfer to the substrate, the RRI process can achieve a pattern transfer without forming an undesirable residual layer, which is typical in other imprint processes. Furthermore, an experimental device for the RRI process is also developed for ink transfer to a flat, flexible substrate. A four-step alignment approach for the preparation of multilayer microstructures (as required in active macroelectronics) is proposed for the RRI, achieving an alignment accuracy of 0.2 mu m and an overlay error of about 5 mu m.