It　has　been　shown　that　activation　of　Notch3　signaling　is　involved　in　the　development　of　pulmonary　arterial　hypertension　(PAH)　by　stimulating　pulmonary　arteries　remodeling,　while　the　molecular　mechanisms　underlying　this　are　still　largely　unknown.　The　aims　of　this　study　are　to　address　these　issues.　Monocrotaline　dramatically　increased　right　ventricle　systolic　pressure　to　39.0　+/-　2.6　mmHg　and　right　ventricle　hypertrophy　index　to　53.4　+/-　5.3%　(P　＜　0.05　versus　control)　in　rats,　these　were　accompanied　with　significantly　increased　proliferation　and　reduced　apoptosis　of　pulmonary　vascular　cells　as　well　as　pulmonary　arteries　remodeling.　Treatment　of　PAH　model　with　specific　Notch　inhibitor　DAPT　significantly　reduced　right　ventricle　systolic　pressure　to　26.6　+/-　1.3　mmHg　and　right　ventricle　hypertrophy　index　to　33.5　+/-　2.6%　(P　＜　0.05　versus　PAH),　suppressed　proliferation　and　enhanced　apoptosis　of　pulmonary　vascular　cells　as　well　as　inhibited　pulmonary　arteries　remodeling.　Our　results　further　indicated　that　level　of　Notch3　protein　and　NICD3　were　increased　in　MCT-induced　model　of　PAH,　this　was　accompanied　with　elevation　of　Skp2　and　Hes1　protein　level　and　reduction　of　P27Kip1.　Administration　of　rats　with　DAPT-prevented　MCT　induced　these　changes.　Our　results　suggest　that　Notch3　signaling　activation　stimulated　pulmonary　vascular　cells　proliferation　by　Skp2-and　Hes1-mediated　P27Kip1　reduction,　and　Notch3　might　be　a　new　target　to　treat　PAH.