Objective To investigate the inhibitory effect of Poecilobdella manillensis (PM) extract on kappa-carrageenan (KCG)-induced tail thrombosis in mice. Methods Kunming mice were intraperitoneally administered PM extract JC-17 (2.5, 25, or 100 mg/kg) or heparin sodium (50 mg/kg) for 7 consecutive days. One hour after the last dose, tail thrombosis was induced by 0.5% KCG injection. Results At 48 h, the tail blackening rate in the Model group was 94.91 ± 3.93%, confirming successful thrombosis induction. The PM-treated groups (L, M, H) exhibited a dose-dependent reduction in tail blackening. The extract significantly prolonged prothrombin time (PT) and reduced fibrinogen (FIB) levels. In the Model group, splenic TNF-α, IL-1β, and IL-6 levels were elevated, with TNF-α reaching the highest concentration (433.8 ± 12.1 pg/mL). All PM-treated groups showed significant suppression of these inflammatory cytokines. Conclusion PM extract effectively inhibits KCG-induced tail thrombosis and exhibits anti-inflammatory activity, suggesting its potential therapeutic value for inflammation-associated thrombotic disorders.