3D-QSAR and Molecular Docking methods were performed on a set of 42 benzimidazolone derivatives considered as inhibitors of the MAPK (Mitogen Activated Protein Kinases) that play critical roles in cell signaling and gene expression. IC₅₀ of 42 compounds is quantitatively modeled by using Multiple Linear Regression (MLR), and Neuronal Networks (NN). The proposed QSAR model has provided statistically significant results (R_MLR = 0.90; R_NN =0.92 and R_CV =0.91), It is validated by leave-one-out method. The general interaction mode of molecules to the P38 Kinases binding sites was explored by using Molecular Docking techniques. In this paper we are focused on the most active molecules of our set, compound 34, and has been compared by the 4-[5-(4-fluoro-phenyl)-2-(4-methanesulfinyl-phenyl)-3H-imidazol-4-yl]-pyridine that is highly interactive with the site P38 alpha Mitogen Activated Protein kinases.