Objective To investigate the effect of loss of PSGL-1 on routine blood test results in PSGL-1 knockout (PSGL-1^-/-) mice, and to detect the expression levels of cytokines IGFBP-6, TNF-α and MIP-1γ mRNA in their peripheral blood.Methods To detect the differences in routine blood test results of normal C57/BL/6 mice and PSGL-1^-/- mice. To prepare cDNA from isolated blood mRNA, and to analyze the differences in expression of cytokines TNF-α and MIP-1γ mRNA in peripheral blood of the C57 mice (control) and PSGL-1^-/- mice by real-time PCR. Results Compared with the C57 control mice, the 12-week old PSGL-1^-/- mice showed significantly increased neutrophils (P<0.05), lymphocytes (P<0.01) and total leukocyte counts (P<0.001), and increased expression levels of TNF-α and MIP-1γ mRNA in the peripheral blood (P<0.05). Conclusions Our findings suggest that the loss of PSGL-1 changes the cell counts of peripheral blood in mice. The up-regulation of cytokines MIP-1γ and TNF-α may influence the immune function of the mice.