Controlled release systems, such as polymeric microparticles (MPs), have emerged as a promising solution to extend the bioavailability and reduce dosing frequency for biologic drugs; however, the formulation of these systems to encapsulate highly sensitive, hydrophilic biologic drugs within hydrophobic polymers remains a nontrivial task. Although scalable manufacturing and FDA approval of single emulsion processes encapsulating small molecules has been achieved, scaling more complex double emulsion processes to encapsulate hydrophilic biologics remains more challenging. : Here, we demonstrate that two hydrophilic, low-molecular-weight, recombinant chemokines, CCL22 and CCL2, can be encapsulated in poly(lactic-co-glycolic acid) (PLGA) MPs using a single emulsion method where the proteins are dissolved in an organic solvent during formulation. : As expected, we observed some differences in release kinetics from single emulsion MPs compared to double emulsion MPs, which traditionally have been used to encapsulate proteins. Single emulsion MPs exhibited a substantially reduced initial burst. Importantly, protein released from single emulsion CCL22-MPs also retained biological activity, as determined by a cell-based functional assay. Decreasing particle size or changing the polymer end group from PLGA-COOH to PLGA-OH increased the initial burst from single emulsion MPs, demonstrating tunability of release kinetics for protein-loaded, single emulsion MPs. Finally, to improve scalability and enable more precise control over MP formulations, the single emulsion process was adapted to a microfluidic, continuous manufacturing system, and the resulting MPs were evaluated similarly. : Altogether, this study demonstrates the feasibility of using a single emulsion encapsulation method for at least some protein biologics.