OBJECTIVE: To describe and compare the pulmonary and plasma pharmacokinetics of different oral formulations of chloramphenicol administered as a single dose to healthy adult horses. METHODS: A single dose of chloramphenicol was administered to 6 healthy, university-owned fasted adult horses IV (25 mg/kg), orally as commercial tablets (50 mg/kg), or orally or intragastrically as compounded suspension (50 mg/kg), according to a randomized crossover protocol. Plasma was collected 5, 10, 15, 20, and 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after drug administration. Bronchoalveolar lavage (BAL) fluid was collected after 1, 4, and 8 hours and processed to obtain pulmonary epithelial lining fluid (PELF) and the BAL cell pellet (BALc). Chloramphenicol concentrations were determined by means of liquid chromatography-tandem mass spectrometry in plasma, PELF, and BALc. Data were used for plasma noncompartmental analysis and calculation of apparent PELF and BALc concentrations. RESULTS: Chloramphenicol concentrations were higher in the PELF than in plasma, irrespective of formulation and administration route (IV, orally, or intragastrically). Compounded suspension administered intragastrically yielded higher maximum concentration and drug exposure than administered orally, with a relative bioavailability of 79%. After oral administration, no significant differences were found between compounded suspension and commercial tablets. CONCLUSIONS: Oral administration of chloramphenicol achieved pulmonary concentrations ≥ 2 and 4 µg/mL for at least 4 hours (50% to 75% of a 6- to 8-hour dosing interval) in 4 out of 5 treated horses. CLINICAL RELEVANCE: Pulmonary pharmacokinetics can be used by practitioners to judiciously select an antimicrobial for the treatment of complex equine pneumonia cases.