The electrostatic features impacting the inhibitory effect of chymase inhibitors have been investigated aiming at providing useful information for understanding the structure inhibition relationships of chymase inhibitors. Structures of the most and least active compounds of the training set are optimized along with the three final database hit compounds at B3LYP/6-31G* level. Statistically significant factors such as HOMO, LUMO, and MESP, for all compounds are calculated. According to Fukui's frontier orbital approximation, the frontier orbitals HOMO and LUMO of a chemical species are very important in defining its reactivity. Fukui first recognized the importance of frontier orbitals as principal factors governing the ease of chemical reactions and the stereoselective path while Parr and Yang demonstrated that most frontier theories can be rationalized from DFT.