Abstract: OBJECTIVE To establish a sensitive and specific LC-MS/MS method for investigating the pharmacokinetics characteristic of α-mangostin liposome in mice. METHODS ICR mice were given in tail vein α-mangostin 3 mg·kg^-1. The α-mangostin concentration was determined by LC-MS/MS and pharmacokinetic parameters was calculated. RESULTS The linearity ranged from 5 to 1 000 ng·mL^-1 (r=0.997 6). The detectction of α-mangostin was 5 ng·mL^-1. The RSDs within day and between days were <11%. The main pharmacokinetic parameters of t_1/2, C_max, AUC_0-t, MRT, CL and V_ss were (0.99±0.12)h, (1 524.60±323.82)ng·mL^-1, (645.84±63.74)ng·h·mL^-1, (0.70±0.11)h, (4.80±0.45)mL·h^-1·kg^-1, and (6.80±1.00)mL·kg^-1, respectively. CONCLUSION The precision, accuracy and recovery of the method are found to be adequate for pharmacokinetic studies. The results can provide the basis for future research.