Major findings of the present study were (1) Notch3 was significantly down-regulated in mouse aorta following CLP, (2) Down-regulation of aortic Notch signalling in sepsis was associated with corresponding decrease in aortic MLCK and increase in MYPT1 expression, (3) pre-treatment with DAPT did not improve sepsis-induced vascular hyporeactivity to NA or CaCl2, rather significantly attenuated the response to these vasoconstrictors in SO mice, (4) treatment with 1400 W reversed attenuated Notch3 expression without significantly altering Jag1 and MLCK expression in septic mouse aorta. Here, NOTCH3 is linked to Sepsis.