Although it has been established that polysaccharides have an effect on bone marrow haematopoiesis, it remains unclear how polysaccharides regulate bone marrow haematopoiesis during absorption and metabolism in vivo . In this study, the effect of a longan polysaccharide of large molecular weight (TLPL) on the gut microbiota of mice and its implications for the haematopoietic process in bone marrow was discussed. Here, the results show that after 21 days of TLPL consumption, the respective quantities of white blood cells, platelets, hemoglobin and bone marrow nucleated cells were determined to be 3.18 ± 1.71 (10 9 L -1 ), 1238.10 ± 164.41 (10 9 L -1 ), 135.10 ± 4.95 (g L -1 ), and 1.70 × 10 7 , which reached 56.98%, 117.28%, and 47.74%, respectively, of the results for NC. TLPL both increased the thymus and spleen indexes by up to 2.08 ± 0.64 (mg g -1 ) and 6.49 ± 2.45 (mg g -1 ), respectively. Additionally, TLPL remodeled the gut microbiota with a significant increase in Lactobacillus in particular, and a significant increase in the level of the potential intestinal metabolite lactate was detected in the serum. Most importantly, a similarly significant up-regulation of the gene expression of the lactate receptor, Gpr81, in the myeloid cells was observed. These changes contributed to the activation of the secretion of various cytokines associated with haematopoiesis, with the levels of G-CSF, EPO, SCF and PF4 increased by 2.44 times, 1.14 times, 1.56 times and 1.13 times, respectively, compared to the MC group, which subsequently accelerated production of bone marrow cells and blood cells. The findings of this study reveal the unique mechanism of dried longan polysaccharides in ameliorating myelosuppression and provide a feasible strategy for the treatment of chemotherapy-induced myelosuppression with bioactive polysaccharides.