The importance of reelin for cortical lamination in the developing CNS is well established, but its role in nerve fiber growth is not well understood. In this study, hippocampal slices were co-cultured with entorhinal slices of GFP mice, in order to compare the growth of the entorhino-hippocampal path in wild type and reeler mice. On day 6, regenerated fibers were seen to navigate from the entorhinal cortex into the hippocampus. The results showed that in wild type mice, regenerated fibers grew along the molecular layer of the dentate gyrus, and only a few fibers were found to penetrate through the granular layer into the hilus. This specific orientation was similar to the perforant path in vivo. Compared with perforant path regeneration in wild type mice, reeler mice seemed to have lost their specific orientation and proper termination in the hippocampus. Without the guidance signal from reelin, the regenerated fibers left the molecular layers and continued to grow aberrantly, i.e., in the granular layer, hilus, pyramidal layer and even stratum oriens. Particularly in the dentate gyrus, the fibers meandered around the cells in the hilus and resembled a network. The study concludes that reelin also serves as an important guidance signal for neuroregeneration of the perforant path.