An increasing number of applications of silver nanoparticles in industry, medicine and everyday life means that the risk of exposure of the human organism to their potential harmful influence is growing. This study has sought to assess the effect of 28-day alimentary administration of different concentrations (0.25, 2.5 and 25 ppm) of a commercial silver nanocolloid on the proliferative activity and synthesis of cytokines by mouse splenocytes. All of the analyzed doses of the colloid had a significant, albeit different, effect on the activity of splenocytes. At the lowest dose, a significant decrease in the proliferation of T cells and more intensive synthesis of pro-inflammatory cytokines, both by non-stimulated and LPS-stimulated cells, was observed. The intermediate dose, on the other hand, stimulated proliferation of B cells while producing a pro-inflammatory effect regarding the synthesis of cytokines. Finally, the highest dose decreased the synthesis of cytokines by non-stimulated cells, but after LPS stimulation, through the strong activation of the IL-10 synthesis, it raised the proliferation of B cells and decreased the synthesis of pro-inflammatory cytokines. The results suggest that silver nanoparticles administered orally have an easy access to the peripheral organs of the immune system, such as the spleen, but the effect of long-term exposure of this organ to the effect of silver nanocolloid depends on several factors, including the dose of nanoparticles, and seems as difficult to predict.