Spinal cord injury (SCI) involves both primary and secondary damages. After the phase of primary injury, a series of inflammatory responses initiate, which belong to the secondary injury. There has been little investigation into the cellular inflammatory response of the spleen to SCI. To disclose the impact of SCI on the spleen, we examined the inflammatory reactions of the spleen during the acute phase of SCI in rat. Adult rats were used as experimental animals and divided into un-injured, sham, and SCI groups (n = 36). Contusion injuries were produced at the T3 vertebral level. Spinal cords were harvested 6 h, 24 h, 48 h, 72 h, 120 h, and 168 h after surgery and were prepared for immunohistochemistry. Spleen wet weight was measured. Blood and spleens were prepared for quantitative analyses. The spleen index was significantly decreased in the SCI groups. Immunohistochemical results showed an increase of the infiltrating cells in the spinal cord tissues from SCI rats at all time points, peaking in 72 h post injury. In the blood, T and B lymphocytes significantly decreased in the SCI group as compared with the sham group, while monocyte increased. Surprisingly, in the SCI group, neutrophil initially decreased and subsequently tended to return toward baseline levels, then remained elevated until the end of the study. Spleen analyses revealed a significant increase in monocyte and neutrophil but a minor (not statistically significant) reduction in T and B lymphocytes. Our data show that the four most prevalent inflammatory cells infiltrate the spinal cord after injury. Increased levels of inflammatory cells (monocyte and neutrophil) in the blood and spleen appear to be very sensitive to SCI. The spleen plays a critical role in the acute phase of SCI.