Angelica polysaccharides (APs) has been used for many years in clinical practice and in blood invigoration. In this article, we want to elucidate the molecular mechanism underlying the effects of APs in the recovery of anemia. Red blood cell count and hemoglobin level in peripheral blood were measured using a fully automatic blood cell counter. Flow cytometry was performed to detect the changes in red blood cell counts and number of T cells in peripheral blood and the spleen. Western blotting was performed to detect Stat5, Bcl-2, and Cyclin D1 protein expression in peripheral blood.The red blood cell count and hemoglobin levels decreased in 5-Fu group compared with the control group (P < 0.05). 5-Fu+APs group showed a marked increase in the number of erythrocytes and a significant increase in hemoglobin content (P < 0.05). Compared with the control group, 5-Fu group showed a significant decreased in the number of CD71/Ter119-labeled erythrocytes (P < 0.001) and CD4/CD8-labeled T cells (P < 0.001) in peripheral blood and the spleen of mice, which was restored significantly in the number of CD71/Ter119-labeled erythrocytes and CD4/CD8-labeled T cells in 5-Fu+APs group (P < 0.001). Compared with the control group, 5-Fu group showed significantly downregulated Cyclin D1 (P < 0.001), Stat5 (P < 0.01), and Bcl-2 (P < 0.05) expression in peripheral blood cells, and it was restored in 5-Fu+APs group (P < 0.05).APs promoted erythrocyte proliferation and increased hemoglobin content. The possible mechanism is by increasing Cyclin D1, Stat5 and Bcl-2 protein expression.