Particles with tailored geometries have received significant attention due to their specific interactions with biological systems. In this work, we examine the effect of polymer capsule shape on cytokine secretion by human monocyte-derived macrophages. Thiolated poly(methacrylic acid) (PMA(SH)) polymer capsules with different shapes (spherical, short rod-shaped, and long rod-shaped) were prepared by layer-by-layer assembly. The effect of PMA(SH) capsule shape on cellular uptake and cytokine secretion by macrophages differentiated from THP-1 monocytes (dTHP-1) was investigated. PMA(SH) capsules with different shapes were internalized to a similar extent in dTHP-1 cells. However, cytokine secretion was influenced by capsule geometry: short rod-shaped PMA(SH) capsules promoted a stronger increase in TNF-alpha and IL-8 secretion compared with spherical (1.7-fold in TNF-alpha and 2.1-fold in IL-8) and long rod-shaped (2.8-fold in TNF-alpha and 2.0-fold in IL-8) PMA(SH) capsules in dTHP-1 cells (capsule-to-cell ratio of 100:1). Our results indicate that the immunological response based on the release of cytokines is influenced by the shape of the polymer capsules, which could be potentially exploited in the rational design of particle carriers for vaccine delivery.