Rhodopsin serves as the prototype for studies of the G-protein coupled receptor (GPCR) proteins as it is the only GPCR protein with known crystal structures, and its structure has been used as the template to model a large number of GPCR proteins, including many used as drug targets. Understanding ligand entrance routes is important for designing drugs with improved efficacy. Here we simulated the egress of the retinal chromophore from the protein by applying the random acceleration molecular dynamics (RAMD) method. The interhelical clefts near the extracellular side were identified to be the predominant egress, while the movement of retinal deep into the cytoplasmic side was also observed. These results suggest possible routes for ligands to enter into the binding pockets of GPCR proteins. In addition, the RAMD simulation results revealed the high stability of the interactions between helix 3 and other helices.