Abstract: OBJECTIVE To investigate the antithrombotic and cardiac function improvement effects of wall-broken Ganoderma lucidum spore powder (BGLSP) and wall-removed Ganoderma lucidum spore powder (RGLSP) by zebrafish model. METHODS Firstly, the ultraviolet and visible spectrophotometry method was employed to determine the contents of total polysaccharide and triterpenoids in BGLSP and RGLSP. Secondly, the drug toxicity test was conducted in wild-type AB strains of zebrafish to determine the maximum tolerable concentration of BGLSP and RGLSP. Then, zebrafish thrombosis models were induced with phenylhydrazine, arachidonic acid, and ponatinib, respectively, and treated with various concentrations of BGLSP, RGLSP or positive drugs. After modeling, O-anisidine was used for staining, and NIS-Elements DTM image processing software was used for image analysis to calculate the staining intensity of zebrafish heart red blood cells and effect on preventing thrombosis. Moreover, the verapamil was used to establish a zebrafish heart failure model. The zebrafish heart enlargement area, venous congestion area, cardiac output, and blood flow velocity were measured to quantitatively evaluate the cardiac function improvement of verapamil-induced zebrafish heart failure. RESULTS The contents of polysaccharides and triterpenoids of RGLSP were significantly higher than those of BGLSP(P<0.001), with fold change of 11 and 5, respectively. The staining intensities of erythrocytes in the heart were significantly increased after induction by phenyl hydrazine, arachidonic acid, ponatinib or verapamil(P<0.01 or P<0.001), respectively. Compared with the model control group, high dose group of BGLSP could significantly inhibit phenylhydrazine and prnatinib-induced zebrafish thrombosis(P<0.05), and could improve the heart enlargement improvement rate, cardiac output increase rate of zebrafish with heart failure(P<0.05 or P<0.01); low and middle dose group of RGLSP showed protective effect on phenylhydrazine, arachidonic acid and prnatinib-induced zebrafish thrombosis, and verapamil-induced zebrafish heart failure(P<0.05 or P<0.01 or P<0.001), and the antithrombotic and anti-heart failure effect of RGLSP was better than that of the same dosage of BGLSP. CONCLUSION BGLSP and RGLSP have markedly protective effect on thrombosis and heart failure, the effect of RGLSP were better than BGLSP, which may be related to its higher content of active components.