In HIV infections, homoeostasis of T cells is dysregulated such that there is a depletion of CD4+ T cells and a progressive loss of naive CD4+ and CD8+ T cells. Methodologies that can improve the function of some or all of these cells will likely enhance immune responsiveness in HIV infection. Interleukin-7 (IL-7) is a cytokine that has been shown to be critical in homeostatic expansion of naive CD8+ and CD4+ cells in lymphopenic hosts, as well as regulating effector T cell to memory T-cell transition and memory T-cell homeostasis. In animal studies and clinical trials, repeated injections of IL-7 are used to boost both CD4+ and CD8+ cell counts. Daily injections, however, are painful, inconvenient, and provide a frequent route for pathogen entry. We developed a poly (D,L-lactide-co-glycolide; PLGA) microparticle controlled release system to administer IL-7 in which a single injection of microparticles can provide therapeutic delivery of IL-7. IL-7 encapsulated PLGA microparticles were first synthesized using a water/organic/water double emulsion method, release from the particles was then optimized using in vitro release studies and therapeutic effectiveness was finally studied in animal studies. These PLGA microparticles showed effective delivery of IL-7 for 1 week in vitro. These results were translated to in vivo delivery as well, which was followed for 9 days. Controlled release of IL-7 in mice demonstrated biological activity in both CD4+ and CD8+ T cells in mice, which was consistent with previously reported results using daily injections. Biotechnol. Bioeng. 2012; 109:18351843. (C) 2012 Wiley Periodicals, Inc.