In order to develop the pomelo industry and improve the utilization of pomelo fruit, in this study, the crude polysaccharide from pomelo fruitlets (PFCP) was extracted by ultrasound-assisted enzymatic method, with a PFCP yield of 9.12%. Scanning electron microscope analysis, particle size analysis, infrared spectrum analysis, and gas chromatography analysis were used to characterize the structure of PFCP. The results showed that PFCP was a heteropolysaccharide with a molecular weight of 3.31 ku, a particle size of 101 μm, and a porous network of spatial structure. The PFCP was composed of rhamnose, arabinose, galactose, glucose, mannose and galacturonic acid in a molar ratio of 0.056:0.138:0.463:0.059:0.186:0.285 with benzene and pyran rings, in which -OH, C=O, C-O, C=C, and N-H structures were contained. In addition, by RAW 264.7 cells model, PFCP has no significant toxic at the range from 62.5 μg/mL to 1000 μg/mL. In terms of cytokine expression, PFCP can effectively promote the expression of three cytokines: NO, TNF-α, and IL-6 in a dose-dependent manner. Among them, the expression of cytokines was the highest at 1000 μg mL of PFCP, and the expression of NO was 42.87 μM, the secretion of TNF-α was 14759.47 pg/mL, and the expression of IL-6 reached 62.20 pg/mL, indicating that PFCP has immune activity. This study may provide some useful information for the pomelo industry.