It is known from the specialty literature that many biological processes, like: bone and vascular remodeling, carcinogenesis, renal function, cardiac hypertrophy, gastrointestinal homeostasis, and reproductive function, are closely related to EP4 signaling. This protein is one of the four receptor subtypes identified for prostaglandin E2 (PGE2), namely: EP1, EP2, EP3 and EP4, which belong to the larger class of G-protein-coupled receptors. In this work, a previously reported homology model of EP4 was used for docking studies of potent EP4 ligands, in order to provide information about protein - ligand interaction patterns. Glide software, from the Schrödinger package, with XP extra precision option, was used for docking simulations. Among the amino acids residues from the EP4 binding site that made interactions with the ligands taken in our study, the key residue Ser285 (highlighted, also, in mutagenesis studies) was noted. The observed interactions between ligands and amino acid residues consist in several hydrogen bonds (e.g. with Thr175, His181, Ser95, Ser103, Asp311) and hydrophobic interactions (e.g. with Ala314, Tyr186). The outcome resulted from the docking studies led to a better understanding of how the agonists and antagonists bind in situ and may lead to the discovery of selective and new active compounds.