Omega-3 polyunsaturated fatty acid (PUFA) may benefit humans and animals with chronic inflammatory diseases. Omega-3 PUFA supplementation improves clinical signs, lung function, and airway inflammation in horses with recurrent airway obstruction (RAO) and inflammatory airway disease (IAD). Eight research horses and 35 client-owned horses. A pilot study examined the dose of PUFA that can alter plasma PUFA composition. Then, a randomized, controlled clinical trial was performed in horses with RAO and IAD. Horses were fed a complete pelleted diet with no hay and randomly assigned to 1 of 3 daily treatments for 2 months: 30 or 60 g of the supplement or 30 g of placebo. Clinical signs, lung function, plasma PUFA composition, and bronchoalveolar lavage fluid (BALF) cytology were evaluated. Data were expressed as median (25-75th percentiles). P < .05 was considered significant. Polyunsaturated fatty acid supplementation resulted in increased plasma docosahexaenoic acid (DHA) that peaked at 4 weeks. Clinical improvement was noted in all horses involved in the clinical trial, but the group that received PUFA had greater improvement in clinical signs (cough score improved 60%), lung function (respiratory effort decreased 48%), and BALF (neutrophils decreased from 23 to 9%) when compared to placebo (cough score improved 33%, respiratory effort decreased 27%, BALF neutrophils increased from 11 to 17%; P < .05). Feeding horses with RAO and IAD a PUFA supplement containing 1.5-3 g DHA for 2 months provides an additional benefit to low-dust diet. Copyright © 2014 by the American College of Veterinary Internal Medicine.