The nucleophilic substitution reaction rate of carboxylic ester is influenced by the structures of leaving group (LG), non-leaving group (NLG) of carboxylic ester and the nucleophile (Nu). A large number of apparent second-order rate constants (kN) were colletcd and analyzed, which of nucleophilic substitution reactions between structurally diverse carboxylic esters and a variety of nucleophiles. Based on the mechanism of nucleophilic substitution reaction, the polarizability effect index PEI(NLG) and group volume index GVI(NLG) of non-leaving group, the ratio of group volume index of nucleophile to that of the leaving group GVI(Nu)/GVI(LG), the difference between pKa of the conjugate acid of nucleophile and that of leaving group (pKa(Nu)-pKa(LG)), were employed to characterize the structures of non-leaving group, leaving group and nucleophile. logkN of 73 nucleophilic substitution reactions were correlated to the structural descriptors mentioned above, and multiple linear regression model was established with good performances. The parameters used in the model were simple and had clear physical meanings. This study provided a theoretical basis for quantitatively estimating the nucleophilic substitution reaction rate of carboxylic esters from molecular structures.