This study aimed to examine the pharmacokinetic changes in tolfenamic acid administered intravenously and orally to ducks at different doses (2, 4, and 8 mg/kg). Furthermore, the binding ratio to plasma proteins was assessed utilizing the ultrafiltration method. Eighteen male Pekin ducks were randomly assigned to three dosage groups (2, 4, and 8 mg/kg), with each group undergoing a trial in two phases: intravenous (IV) and oral administration. The sample was analyzed using an approved HPLC-UV method. A non-compartmental analysis was utilized to evaluate the pharmacokinetic data. For 2 mg/kg IV injection, the area under the curve from zero to infinity (AUC0-∞), total clearance (ClT), volume of distribution at steady state (Vdss), and elimination half-life (t1/2ʎz) were 13.03 h*µg/mL, 0.15 L/h/kg, 0.30 L/kg, and 1.72 h, respectively. Following oral administration at a dose of 2 mg/kg, the AUC0-∞, peak plasma concentration (Cmax), and bioavailability were 6.32 h*µg/mL, 2.25 µg/mL, and 48.52%, respectively. The t1/2ʎz was extended, Cmax and AUC0-∞ elevated, Tmax shortened, and ClT decreased in a dose-dependent manner. No dose-related change was observed in Vdss and bioavailability. In ducks, tolfenamic acid’s plasma protein binding was 99.74%, unaffected by concentration. These results may contribute to the application of tolfenamic acid in ducks at different doses, but dose-related changes in therapeutic efficacy should also be demonstrated.