OBJECTIVE: To establish a method for the simultaneous concentration determination of saxagliptin and its metabolite 5-hydroxy saxagliptin in diabetic model rats in vivo. METHODS: UPLC-MS/MS was performed on the column of Waters BEH Shield RP18 with mobile phase of 10 mmol/L ammonium acetate-acetonitrile (70 ∶ 30, V/V) at a flow rate of 0.3 mL/min, column temperature was 30 ℃, and injection volume was 10 μL. Scanning mode was multi-reactive monitoring with positive ion mode, and each ion pair was m/z 316.2→180.2 (saxagliptin), m/z 332.3→196.2 (5-hydroxy saxagliptin) and m/z 304.2→153.9 (vildagliptin, internal standard). 6 SD rats were selected and intragastric administred saxagliptin 0.53 mg/kg after inducing diabetic models. Blood sample 0.25 mL was taken from eyes before administration and after 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 12.0, 24.0 h of administration. Plasma concentration of saxagliptin and its metabolite 5-hydroxy saxagliptin were determined, and Win Nonlin 6.1 software was used to calculate the pharmacokinetic parameters. RESULTS: The mass concentration of saxagliptin and 5-hydroxy saxagliptin ranged in 0.1-100, 0.2-200 ng/mL(r=0.997 2, 0.996 5); limits of quantitation were 0.1, 0.2 ng/mL; inter-day and intra-day RSDs were less than 12% (n=5, 3); accuracy was 94.1%-105.4%, 91.0%-103.6%; extraction recoveries were 72.4%- 87.3%, 107.0%-115.3% (RSD<13.6%, n=6); matrix effects were 105.9%-107.8%, 83.5%-88.2% (RSD<10.3%, n=6);RSD of stability was less than 11.0%(n=5), respectively; and pharmacokinetic parameters as cmax were (49.97±11.14), (16.87±7.35) ng/mL, t1/2 were (2.88±0.21), (4.21±0.95) h, AUC0-24 h were (90.95±7.06), (49.13±5.33) ng·h/mL (n=6). CONCLUSIONS: The method is simple, accurate, specific, and suitable for the pharmacokinetics research of saxagliptin and its metabolite 5-hydroxy saxagliptin in diabetic rats in vivo.