Abstract: OBJECTIVE To establish an HPLC-MS/MS method for the determination of the concentration of lisinopril in human plasma , and to study its pharmacokinetics , to provide evidence for its clinical application. METHODS Twenty healthy volunteers were orally given a single dose of 20 mg lisinopril tablet and the plasma concentration of lisinopril was determined by HPLC-MS/MS. Then DAS software was used to fit the plasma concentration-time data and to calculate the pharmacokinetic parameters, the compartment model was discriminated by AIC. RESULTS The calibration curve was linear within the range of 2.0-200 ng·mL^-1(r=0.997 5), the recovery was 88.8%, and the RSD of intra-day and inter-day were less than 6.62% and 13.0%, respectively. The optimal compartment model fitted to single compartment model (Wi=1/C2 , AIC=4.61). The pharmacokinetic parameters were as follows: t_1/2 was (10.91±3.71) h, t_max was (6.65±1.50) h, C_max was (98.15±23.66) ng·mL^-1, Ka was (0.83±1.28) h-1, Vd/Fwas (220.70±62.82)L, AUC_0-72 was (1 437.41±399.68) ng·h·mL^-1, AUC_0-∞ was (1 516.54±376.83)ng·h·mL^-1, respectively. CONCLUSION The method is suitable to determine the concentration of lisinopril in human plasma and clinical studies because of its convenient, specificity, sensitive.