Objective: To study the anti-gout effect of active ingredients in Poecilobdella manillensis. Methods: Hypoxanthine was used to replicate mouse model of hyperuricemia, and xylene was used to induce mouse auricle swelling model. The hot plate method and writhing method were used to screen the active site of Poecilobdella manillensis, and then the active ingredients were screened. The material basis of anti-gout effect of Poecilobdella manillensis was observed. Results: The water-soluble fraction of Poecilobdella manillensis was the active site against gout, which could reduce the level of serum uric acid in hypoxanthine-induced hyperuricemic mice and inhibit xylene-induced auricular swelling in mice, deduce acetic acid-induced writhing reaction in mice and increase the hot plate pain threshold in mice; Hirudin was the main active ingredient in water-soluble parts. Poecilobdella manillensis active ingredient 0.8 g/kg and 0.4 g/kg and Poecilobdella manillensis residue 2.0 g/kg could significantly reduce serum uric acid levels. The serum uric acid levels decreased from232.73 ± 50.93 umol/L in model group to 140.70 ± 25.97 umol/L, 149.07 ± 39.28 umol/L, 176.45 ± 44.33 umol/L, respectively (P ＜ 0.01) . Poecilobdella manillensis active ingredients 0.8 g/kg, 0.4 g/kg and 0.2 g/kg and Poecilobdella manillensis residue 2.0 g/kg could significantly inhibit xylene-induced ear auricle swelling in mice. The swelling degree was inhibited from 22.80 ± 2.86 mg to 20.10 ± 2.18 mg, 19.80 ± 2.57 mg, 20.10 ± 1.66 mg and 20.85 ± 1.60 mg respectively (P ＜ 0.05) . Poecilobdella manillensis 0.8 g/kg active ingredient could significantly reduce the number of writhing mice caused by acetic acid. The number of times was reduced from 22.80 ± 2.86 times to 20.10 ± 2.18 times (P ＜0.05) . Conclusion: Poecilobdella manillensis anti-gout activity is in water-soluble parts, and Hirudin is the main active ingredient.