The medial (MEC) and the lateral (LEC) regions of the entorhinal cortex send a major input to the hippocampus and have been proposed to play a foremost role in combining spatial and non-spatial attributes of episodic memory. In addition, it has been recently suggested that the MEC is involved in the processing of information in a global reference frame and the LEC in the processing of information in a local reference frame. Whether these putative functions could be generalized to navigation contexts has not been established yet. To address this hypothesis, rats with MEC or LEC NMDA-induced lesions were trained in two versions of a navigation task in the water maze, a global cue condition in which they had to use distal room cues and a local cue condition in which they had to use 3 objects placed in the pool. In the global cue condition, MEC-lesioned rats exhibited slower acquisition and were not able to precisely locate the submerged platform during the probe trial. In contrast LEC-lesioned rats exhibited control-like performance. In the local cue condition, navigational abilities were spared in both lesion groups. In addition when the 3 different objects were replaced by 3 identical objects, all groups maintained their navigation accuracy suggesting that the identity of objects is not crucial for place navigation. Overall, the results indicate that the MEC is necessary for place navigation using a global reference frame. In contrast, navigation using a local reference frame does not require the LEC nor the MEC.