BACKGROUND: Glass polyalkenoate cements (GPCs) are bio-adhesives which consist of ionomeric glass particles embedded in a poly-salt matrix. These materials have been used in dentistry and orthodontics extensively but are presently being optimized as bone putties for orthopedic applications. OBJECTIVE: This study utilized a patented ionomeric glass (mole fraction: SiO2:0.48, ZnO:0.36, CaO:0.12, SrO:0.04) to formulate two GPCs: GPC A (<45 μm particle size glass) and GPC B (45 μm-63 μm). These formulations were previously assessed for their effect on osteoblast viability and osteogenic function. However, the immunomodulatory effects of GPC A and B have not previously been investigated. METHOD: Non-toxic concentrations of (a) GPC dissolution products and (b) fragmented GPC particles were tested for their ability to affect the secretion of cytokines (TNF-α, IL-1β, IL-6 and IL-10) by rat peripheral blood mononuclear cells (PBMCs), in the presence or absence of the stimulant liposaccharide (LPS). Additionally, the ionic concentrations of Sr, Zn, Ca, and Si were measured in GPC ionic extracts, and the size, shape and concentration of fragmented GPC particles in deionized water were characterized using an optical microscope-based particle analyzer. RESULTS: The results showed that GPC A ionic products reduced the concentration of TNF-α secreted by stimulated cells compared with cells stimulated in the absence of GPC products. Interestingly, the particles released from GPC A significantly increased the secretion of both TNF-α and IL-6 from unstimulated cells, compared to control cells. CONCLUSION: Neither GPC B ionic products nor released particles were found to be biologically active with respect to PBMC cytokine secretion.