Asian sand dust (ASD), a type of particulate matter found in Asia, migrates to East Asia. The increased airborne spread of ASD has led to concerns regarding possible adverse health effects. Our group previously reported that ASD induces lung inflammation in mice, but it is still unclear whether ASD affects lymphoid organs. In this study, we investigated the effect of ASD on splenocytes in a mouse model of ASD exposure. ICR mice were intratracheally administered a single dose of normal saline (control) or ASD and were subsequently sacrificed 1 or 3 days later. TNF-α production in bronchoalveolar lavage fluids was higher at day 1, but not at day 3, after ASD administration. The enzyme-linked immunosorbent assay results showed that ASD administration increased mitogen-induced IL-2, TNF-α, and IL-6 production in splenocytes. Additionally, cell viability assay showed enhanced splenocyte proliferation at day 3, but not at day 1, after ASD administration. The electrophoretic mobility shift assay results demonstrated that nuclear factor κB (NF-κB) was activated in splenocytes on day 3, but not on day 1. In particular, NF-κB activation was detected in CD4+ and CD11b+ cells on day 3. These results suggest that ASD induces subacute inflammatory responses with NF-κB activation in the spleen, in contrast to acute inflammation in the lungs. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 549–558, 2015.