Abstract: In order to investigate the optimal extraction process of crude polysaccharide from Guliao tea and evaluate its immunomodulatory activity, Guliao tea as the raw material and fixed the ultrasonic power at 400 W, the effects of parameters including ultrasonic time, extraction temperature, extraction times and solid-liquid ratio on the yield of Guliao tea crude polysaccharide were examined. The parameters were optimized by Box-Behnken response surface design. The impact of Guliao tea crude polysaccharide on the proliferation activity of RAW264.7 murine macrophages was detected by CCK-8 assay. The secretions of TNF-α, IL-6 and NO were measured to evaluate immunomodulatory activity. The results indicated that the highest yield of Guliao tea crude polysaccharide was 13.12%±0.11% under the conditions of 32 min of ultrasonic time, 64 ℃ of extraction temperature, four extraction circles and a 1:44 g/mL solid-liquid ratio. The total sugar amount in the crude polysaccharide from Guliao tea was 61.8%±0.09%. Guliao tea crude polysaccharide exhibited a slight effect on the proliferation activity of RAW264.7 murine macrophages with essentially no toxicity and demonstrated a dose-response relationship in promoting the secretion of TNF-α, IL-6, and NO within the range of 50~400 μg/mL. By optimizing the extraction process of crude polysaccharide from Guliao tea and evaluating its immunomodulatory activity, the study provided a scientific basis for more effective exploration and utilization of Guliao tea polysaccharide.