Abstract: Cortisol is involved in a number of physiological and oxidative processes, including functional regulation in human milk. This hormone has been widely used for several therapeutic approaches. The aim of this study was to evaluate the immunomodulatory effect of Polyethylene Glycol (PEG) microspheres with adsorbed cortisol on the functional activity of colostrum phagocytes. The PEG microspheres were evaluated by flow cytometry and fluorescence microscopy were determined in colostrum phagocytes the effects of the PEG microspheres with adsorbed cortisol on the viability, superoxide release, phagocytosis, microbicidal activity and intracellular calcium release. The fluorescence microscopy and flow cytometry analyses revealed that the cortisol was able to adsorb PEG microspheres. The phagocytes display an increased release of superoxide in the presence of PEG microspheres with adsorbed cortisol. PEG microsphere adsorbed cortisol increased the phagocytosis and mediated bacterial killing by colostral mononuclear phagocytes. The cortisol adsorbed to PEG microspheres had direct effect on colostrum phagocytes and that they were able to increase the intracellular calcium release of colostrum phagocytes. These findings suggest that PEG microspheres with adsorbed cortisol present immunostimulatory effects in colostrum phagocytes and thus, these PEG microspheres have potential for future clinical applications in the infection process.