Purpose: Epidemiological studies support the hypothesis that dietary omega-3 long chain polyunsaturated fatty acids and carotenoids prevent from Age-related Macular Degeneration (AMD). AREDS2 failed to find benefits of omega-3 supplementation on the progression to advanced AMD. However, lower risk progression was reported in AMD patients of the NAT2 study whom omega-3 incorporation in red blood cells and plasma was the highest. Our purpose was to test whether feeding mini-pigs with encapsulated docosahexaenoic acid (DHA) and lutein would promote the bioavailability of the nutrients in plasma and tissues including the retina. Methods: Microparticles containing lutein and DHA were formed by stabilized water-in-oil emulsions. Eight mini-pigs (Ellegaard Goetingen, 8-10 months-old) were fed during 3 months with 641mg of DHA + 5.1mg of lutein daily present in either non-encapsulated forms (n=4) or microparticles (n=4). Two animals fed with standard chow were used as controls. Plasma was collected at 1, 2 and 3 months. The retina, brain, muscles, liver, adipose tissue were collected and further analyzed for fatty acid and carotenoid contents. Results: Feeding the mini-pigs with encapsulated nutrients promoted plasma DHA incorporation at 1 month of feeding: 22.7±1.4 vs 44.9±3.0mg DHA/mL of plasma. While plasma lutein remained undetectable in mini-pigs fed with non-encapsulated nutrients at any time in the fasting state, lutein reached its highest level of 0.29±0.07ng lutein/mL of plasma in the experimental group at 1 month. DHA was increased in muscle, liver, adipose tissue and red blood cells by 2 to 5-fold in mini-pigs fed with non-encapsulated DHA, and by 3 to 7-fold in the animals fed with microparticles, when compared to mini-pigs fed with standard chow. Neither DHA nor lutein content was improved in the retina and brain of any of the groups of mini-pigs. But a significant increase of the precursors of DHA: EPA and DPA was observed in the retina and brain of minipigs fed with microcapsules. Conclusions: Our pre-clinical study in mini-pigs validated the technology of nutrient microencapsulation for increasing the bioavailability of DHA and lutein in plasma, but not in the retina. This negative effect in the retina is consistent with previous data in human samples suggesting that circulating DHA marginally participate to DHA in the retina.