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To study the effect of qinglongyi polysaccharide on cation concentration in erythrocyte of S180 mice a tumor mouse model was developed, and the mice were treated with high, medium, and low doses of qinglongyi polysaccharide through abdominal injection for 7 d. Erythrocytes were collected and erythrocyte suspensions were prepared. Change of Ca2+ concentration in the erythrocytes of S180 mice was measured by stained with Fluo-3/AM and observed with laser scanning confocal microscope, Change of H+ concentrations measured by stained with BCECF-AM and observed with laser scanning confocal microscope. Results showed Qinglongyi polysaccharide lowered the concentration of Ca2+ and H+ in erythrocytes of S180 mice, which is remarkable compared with negative control group(PLt0.05). Conclusion Qinglongyi polysaccharide can maintain the stability and balance of cation concentration in erythrocyte of S180 mice.