To explore the effect of Galectin-3 (Gal-3) on the proliferation of vascular smooth muscle cells and the stenosis of arteriovenous fistula (AVF) in rats and explore the possible mechanism. Methods Thirty AVF rats were selected and randomly divided into AVF group, citrus pectin group and combination group, 10 in each group. Another 10 rats were sham-operated and set as the sham-operated group. The combination group was given citrus pectin (0.15 mg/kg) by gavage, and epidermal growth factor ［extracellular signal-regulated kinase (ERK) pathway agonist (EGF)］ (10 μg/kg) was injected into the tail vein. In the citrus pectin group, citrus pectin (0.15 mg/kg) was administered by gavage, and an equal volume of PBS was injected into the tail vein. The sham operation group and the AVF group were given the same volume of normal saline, and the same volume of PBS was injected into the tail vein. One time a day. Intervention for 4 weeks. The proliferation ability of vascular smooth muscle cells was detected by MTT method. The levels of serum inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected. The levels of vascular tissue transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) were detected. Western blot was used to detect the protein expressions of p38 mitogen-activated protein kinase (MAPK), p-p38 MAPK, ERK1/2 and p-ERK1/2 in vascular tissue. Results Compared with the AVF group, the absorbance values at 24, 48, and 72 h, serum TNF-α, IL-6 levels, vascular tissue TGF-β1, VEGF levels, p-p38 MAPK/p38 MAPK, p-ERK1 /2/ERK1/2 were decreased in the citrus pectin group (P＜0.05). Compared with the citrus pectin group, the absorbance values at 24, 48, and 72 h, serum TNF-α, IL-6 levels, vascular tissue TGF-β1, VEGF levels, p-p38 MAPK/p38 MAPK, p-ERK1 /2/ERK1/2 were increased in the combined group (P＜0.05). Conclusion Gal-3 inhibitor modified citrus pectin can inhibit the proliferation and inflammatory response of vascular smooth muscle cells, and relieve AVF stenosis, and inhibit the activity of ERK signaling pathway