OBJECTIVE: To study the effects of Danhong injection on the pharmacokinetics of atorvastatin calcium (ATV) in rats. METHODS: The plasma concentration of ATV in rats was determined by UPLC-MS/MS using hydrochloric piperidine as internal standard. The determination was performed on AcquityTM BEH C18 column with mobile phase consisted of 5 mmol/L ammonium formate solution (containing 0.1% formic acid)-methanol (gradient elution). The ion source was ESI, and the mass transfer ratio (m/z) was 559.20→440.20 (ATV) and 264.20→154.05 (internal standard) by multiple reaction monitoring (MRM) mode. A total of 24 SD rats were randomly divided into ATV alone group (ATV, 10 mg/kg), Danhong injection low-dose, medium-dose and high-dose groups (Danhong injection 1, 2, 4 mL/kg+ATV 10 mg/kg). Blood samples were collected at different time points, and plasma concentration was determined and pharmacokinetic parameters of ATV were calculated. RESULTS: The linear range of ATV was 0.25-62.50 ng/mL, and the limit of quantitation was 0.25 ng/mL. RSDs of precision and stability tests were all lower than 15%. Extraction recovery and matrix effect were all higher than 85%. The pharmacokinetic parameter cmax of ATV in Danhong injection medium-dose and high-dose groups were (23.78±6.4), (33.66±8.15) ng/mL, which were significantly higher than (13.99±2.54) ng/mL in ATV alone group (P<0.05). AUC0-24 h of Danhong injection low-dose, medium-dose and high-dose groups were (67.20±15.22), (88.16±14.84), (126.84±31.55) ng·h/mL, which were significantly higher than (46.08±7.47) ng·h/mL in ATV alone group (P<0.05 or P<0.01). CONCLUSIONS: Combined administration of Danhong injection can significantly increase the plasma exposure of ATV in rats.