Objective To compare the effects of genistein, bosentan, and tadalfil in treatment of monocrotaline-induced pulmonary arterial hypertension (PAH) in rats. Methods Monocrotaline-induced PAH SD-rat model was established by injecting monocrotaline (50 mg/kg) intraperitoneally (n=48), while the rats in control group (n=8) were given normal saline injection. Then all model rats were randomly divided into 6 groups (n=8) according to different drugs given by gavage after 3 weeks:PAH group (PAH rats were treated with normal saline), genistein G₃₀, G₆₀, G₁₂₀ groups (PAH rats were treated with genistein 30, 60, 120 mg·kg^-1·d^-1, respectively), bosentan group (PAH rats were treated with bosentan 5 mg·kg^-1·d^-1), and tadalafil group (PAH rats were treated with tadalafil 0.5 mg·kg^-1·d^-1). After 2 weeks of treatment, survival rate, tricupid regurgitation (TR), pulmonary artery diameter (PAD), mean pulmonary arterial pressure (PAP), acetylcholine (ACh)-induced endothelium-dependent relaxation (EDdR), sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EDiR), right ventricular hypertrophy index (RVHI), and lung phathological of rats in each group were compared. Results Compared with the control group, the TR, PAD, mean PAP and RVHI of rats were significantly increased in PAH group (P<0.05). Compared with the PAH group, the TR and RVHI of rats were significantly decreased in G₆₀ and G₁₂₀ groups, PAD was significantly decreased in G₁₂₀ group, mean PAP was significantly decreased in G₃₀, G₆₀ and G₁₂₀ groups, survival rate was significantly increased in G₁₂₀ group, and endothelium-dependent relaxation was significantly improved in G₃₀, G₆₀ and G₁₂₀ groups, while pulmonary vascular luminal stenosis, wall thickening and vascular smooth muscle cell proliferation were significantly inhibited in G₃₀, G₆₀ and G₁₂₀ groups (P<0.05). However, the above effects of genistein were less than bosentan and tadalafil (P<0.05). Conclusion Genistein has a certain effect on monocrotaline-induced PAH in rat; although its efficacy is less than that of bosentan and tadalafil, genistein is cheaper, easy to obtain and has less side effects, and is also expected to be a new auxiliary drug for PAH.