Purpose:: Prostaglandins (PGs) have been found in tears of patients with ocular surface disorders, and are powerful markers of inflammation. The lacrimal gland has been reported to synthesize PGs. Polyunsaturated fatty acids esterified in phospholipids are the precursors of pro- and anti-inflammatory PGs. The aim of this study was to compare the phospholipid content of the lacrimal gland in human and in different rat species. Moreover the changes in fatty acids of the lacrimal glands of Lewis rats were studied after a nutritional intervention. Methods:: Lacrimal glands were excised from Wistar, Sprague-Dawley and Lewis rats (3 month-old) and from Humans 3 to 36 hours after death. Phospholipids were extracted, quantified and separated by HPLC. Phospholipid FAs were analyzed by gas chromatography. Results:: Whereas phospholipids represented the major lipid class in Wistar and Sprague-Dawley rats (73-75%), they accounted for 50% of total lipids in Lewis rats and only 4% in Humans. Phospholipids in Humans contained 40% phosphatidylethanolamine as in Lewis and Sprague Dawley, significantly less phosphatidylcholine and more phosphatidylserine than the 3 rat species (35% versus 41-43% phosphatidylcholine and 8.0% versus 4-5% phosphatidylserine). In the 3 rat species, phospholipids contained 3-5% of n-3 fatty acids and 29-37% of n-6 fatty acids with a ratio n-6/n-3 ranging from 6 to 9. In human, their content varied from one individual to another, probably depending on the diet of the patient, but was comparable to Lewis and Sprague-Dawley rats. A diet enriched with n-3 fatty acids EPA (20:5 n-3) and DHA (C22:6n-3) given to Lewis rats for 2 months significantly increased C20:5n-3 (from 0.3 to 10.8%), C22:5n-3 and C22:6n-3 and decreased C20:4n-6 (from 17.5 to 12.0%), leading to a significant decrease in the n-6/n-3 ratio (from 5.6 to 1.3). Conclusions:: Based on the similarity between Humans and Lewis rats in terms of fatty acid profile of the lacrimal glands and on the ability of the lacrimal glands to dietary changes, dietary fatty acids may be powerful to modulate inflammatory processes in the lacrimal glands in humans, and possibly to reduce ocular surface disorders characterized by inflammation.