Objective To investigate the preventive effect of resveratrol against acute gouty arthritis in mice and whether M2 polarization of macrophage mediates the effect. Methods Eighteen C57BL/6 mice were randomly divided into three groups (n=6):sham group, model+solvent control group, and model+resveratrol group. The right hind limb ankle joint of mice in the sham group were treated with sterile normal saline. The right hind limb ankle joint of mice in the model+solvent control group were treated with DMSO in advance and then with monosodium urate (MSU) crystals to establish acute gouty arthritis model. Mice in the model+resveratrol group were treated with resveratrol dissolved in DMSO in advance and then with MSU crystals to establish acute gouty arthritis model. The bilateral paw thickness of mice in each group was measured and H-E staining was used to observe the inflammation of synovial tissue of feet and metacarpal joints of mice in each group. The primary macrophages from abdominal cavity of normal mice were extracted, treated with resveratrol, and then stimulated with MSU crystals. The expression of M1-polarized macrophage markers inducible nitric oxide synthase (iNOS) protein and the inflammatory indexes tumor necrosis factor α (TNF-α) mRNA and interleukin 1β (IL-1β) mRNA were detected by Western blotting or qPCR. The expression of M2-polarized macrophage markers F4/80 and CD163 were detected by flow cytometry. Results Acute gouty arthritis model of mice was successfully established. The right hind limb thickness of mice in the model+resveratrol group was significantly lower than that in the model+solvent control group ([1.98±0.02] mm vs[2.49±0.12] mm, P<0.01). The infiltration area of neutrophils in synovial tissue of feet and metacarpal joints in mice of model+resveratrol group were also significantly reduced. In vitro, resveratrol significantly inhibited the expression of iNOS protein, TNF-α mRNA and IL-1β mRNA in primary peritoneal macrophages (all P<0.01) and increased the percentage of F4/80⁺CD163⁺ in macrophages (P<0.01). Conclusion Resveratrol may effectively alleviate acute gouty arthritis in mice by promoting M2 polarization of macrophages and inhibiting the expression of inflammatory factors.