To evaluate the alteration of CD47 on RBCs of pigs infected with M. suis, we induced the experimental porcine eperythrozoonosis and collected the blood samples at the different time points. The result of analysis by flow cytometry after reaction with mouse-anti-human CD47 and caprine-anti-mouse IgG-FITC reagents indicated that the CD47 quantity on RBCs changed correlatively with the course of PE. The lowest value of M1 (percentage of the positive cells in fluorescence intensity) occurred on day 7 post inoculation at the peak of parasitemia and decreased 82% compared with the control sample. And then, the values of M1 on day 14 and 21 rised slowly but were still significantly different with the controls (p < 0.01). These suggested that the quantity of CD47 on RBCs altered progressively with the phases of the PE disease. The decrease of CD47 on RBCs maybe weaken the inhibitory CD47-SIRPalpha interaction and provide positive signals for phagocytosis of macrophages resulting in the removal of the RBCs from the circulation. In conclusion, CD47, a marker on RBCs, maybe play an important role on the mechanism of hemolysis caused by infection of M. suis.