The present study was carried for studying the pharmacokinetic of tulathromycin in healthy and febrile feedlot calves. A single dose of tulathromycin (2.5 mg/kg b.w.) was injected subcutaneously to ten Friesian beef calves (5 healthy and 5 febrile) 4 to 6 months of age, weighing 110 to 128 kg. Blood samples were collected after injection from all calves for determination of the concentrationsof the drug by HPLC. Results showed that, the drug was rapidly absorbed reaching the highest plasma concentrations during 2 hours after dosing where C_max, t_1/2el, AUC and MRT was significantly higher in diseased (0.65h; 25.17h, 23.62 µg h ml^_1 and 35.98h) than in healthy calves (0.59h; 24.14h, 20.78µg h ml^_1 and 34.58h) respectively. Tulathromycin concentrations were maintained in the serum of injected calves equal to or higher than the MIC₉₀ of major BRD pathogens (Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis) for about 7 days and in lung tissues at least 10 days especially in febrile ones.