Human CD14 plays an important role in innate immunity by being the key receptor of lipopolysaccharide found on Gram-negative bacteria. The recently discovered widespread localization of CD14 in secretions and mucosal surfaces reveals its extensive anti-microbial properties and numerous potential medical applications. To produce active recombinant human CD14 (rhCD14) for massive distribution, transgenic tobacco plants were successfully generated to express rhCD14 in the seed endosperm under the control of two versions (1.8 kb and 5.1 kb) of the rice glutelin Gt-1 promoter. Plant-made rhCD14 proteins reached a concentration of 16 microg/g of seeds and showed stability, proteolytic resistance to pepsin digestion and ability to induce the release of pro-inflammatory IL-6 and IL-8 cytokines in presence of LPS. The expression of plant rhCD14 in tobacco seeds constitutes a promising low-cost and abundant supply of this immune protein to further investigate its roles in, impacts on and potential medical applications for the innate immune system.