Disseminated intravascular coagulation (DIC), a life-threatening secondary complication in several diseases, is characterized by large amounts of thrombin that lead to fibrin deposition and microthrombus formation throughout the microcirculation. Recent in-vitro studies suggest that crocin, crocetin or safranal, carotenoid constituents of the spice Crocus sativus L. (saffron), have antithrombotic properties, especially anti-Xa activity. The present study was designed to evaluate the effect of crocetin on thrombosis procedure using a rabbit model of bacterial endotoxin-induced DIC. Crocetin administration (3 mg/kg), 30 min before the beginning of endotoxin infusion, improved DIC-related haemostatic indices such as platelet blood counts (P ≤ 0.05), blood plasma fibrinogen and protein C concentration (P ≤ 0.05). In addition, it ameliorated DIC-associated disease and fibrin deposition in the glomeruli (P ≤ 0.05). These results indicate that crocetin reveals a preventive antithrombotic role in vivo and prescribe further investigation on the possibility of developing crocetin-based DIC treatment modalities.