The goal of this study was to clarify the tilmicosin pharmacokinetics in healthy and naturally infected broiler with respiratory disorders (NRI). Tilmicosin achieved its Cmax after 3.01 and 2.63 h (Tmax) of administration, with values of 1.21 and 0.93 μg/ml, respectively, following single intracrop dose (25 mg/kg BW). Tilmicosin t0.5ab was 0.590.034 h & 0.590.02 h and t0.5el was 011.32 & 8.89 h, sequentially. Tilmicosin attained its Cmax following a single intramuscular injection (25 mg/kg BW, IM) after 1.51 & 1.56 h (Tmax), respectively, with values of 1.20 and 1.28 μg/ml. The t0.5ab (0.29 & 0.30 h) and t0.5el (7.07 & 5.04 h) of tilmicosin showed a clear reduction relative to intracrop dosing, serially. Tissue residues after repeated oral (75 mg/L of drinking water for 3 consecutive days) administration revealed a lower significant plasma tilmicosin concentration after all times of sampling in NRI chickens related to those of healthy ones. Tilmicosin residues was assayed in lung, kidney, liver, thigh and breast muscles, after "2h, 24 h, 3d, 5d, 7d, 9d and 11 days post tilmicosin stoppage. The highest residue values were found in the lungs, followed by the liver and kidneys, while the lowest irrelevant values were found in the thigh and breast muscles. Finally, tilmicosin has a fast absorption rate, a long elimination half-life, and substantial blood-to-tissue penetration, particularly in the lungs. Following repeated oral tilmicosin administration, the required withdrawal period is 9 d for thigh and breast muscles and 10 d for internal organs.