Pharmacokinetics drug interactions are one of the most important drug interactions in clinical pharmacology science which can consequently affect the pharmacological activities of drugs. The aim of this research study was to investigate the effect of phenylbutazone on various pharmacokinetics parameters of thiopental in drug interactions in female dogs. On this basis, eight female dogs were randomly divided into two groups (control and test groups). The Biochemical and hematological parameters were measured and were found to be at normal range. Normal saline of 0.9% (0.1 ml/kg) and thiopental sodium of 5% (0.34 ml/kg) were intravenously administered to animals in the control group. Equivalent dose of thiopental sodium was also administered following the injection of phenylbutazone 20% via the same route. Serum was separated by centrifugation and thiopental concentration was measured using HPLC method. Pharmacokinetics factors including rate of elimination, half-life, volume of distribution, and clearance were calculated using non-compartmental analysis of the concentration-time curves. The results of this study showed that in comparison with the control group, half-life, distribution volume of thiopental were significantly increased in the test group (P<0.05). ِElimination rate of the thiopental and clearance was also reduced in test group compared to control group and the difference was significant (P<0.05). Therefore, phenylbutazone can increase half-life and volume of distribution of thiopental in female dog.