The interaction between the role of 18.5 KDa myelin basic protein (MBP) isoform and phospholipids has been thought to maintain the stability and compactness of the myelin sheath structure. In this study, we describe the statistical thermodynamic theory of different concentrations’ effects on MBP in the major myelin lipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE)，and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS)) monolayers at the air/subphase interface via Langmuir-Blodgett (LB) technique. A simple statistical mechanical theory is established that predicts the interaction between proteins and phosphate head groups at low surface pressures and the second virial coefficient dependences for the PC, PE, and PS head groups are illustrated. In addition, the surface pressure(π)-mean molecular area(mma) curves were also analyzed using two-dimensional virial equation of state (2D-VES). The positively charged showed that MBP may integrate into different lipid monolayers via hydrophobic and electrostatic interactions, which was found to be consistent with AFM observations of domain and aggregate structures as well as with changes in the surface morphology induced by MBP. These analyses pertaining to membrane structure will provide better insight into membrane modeling systems, especially the interaction between membrane molecules.