Activation of the sympathetic nervous system leads to an increase release of norepinephrine (NE) during sepsis. Re‐uptake of NE by the NET (NE Transporter) protein is the primary mechanism by which the biological effects of NE in the synapse are terminated. A SNARE protein, Syntaxin 1A plays a major role in presynaptic regulatory mechanism linking neurotransmitter secretion to neurotransmitter reuptake activity. However the role of Syntaxin 1A in the regulation of NE in septic heart is not known. Therefore, in the present study the effect of increased duration of sepsis on the expression of syntaxin1A and NET in heart was elucidated. Male Sprague‐Dawley rats (300–350g) were randomized into sham, 1‐, 3‐ and 7‐day sepsis groups. Sepsis and sham‐sepsis was induced using 200mg/kg cecal inoculum and 5% dextrose water i.p., respectively. Hearts were isolated to perform the RT‐PCR and immunoblot analyses for Syntaxin 1A and NET levels. Syntaxin 1A mRNA as well as protein expression increased significantly at 1‐day, while reduced at 3‐ and 7‐day post‐sepsis. NET gene expression was not altered significantly in septic animals but NET protein expression was decreased (61%) in 3‐day post‐sepsis group. We also observed increased NE levels (50% compared to sham) at 1‐day post‐sepsis. The data suggest that the elevation of Syntaxin 1A could be responsible for an increased level of myocardial NE at 1‐day post‐sepsis. Disruption of the transporter function at 3‐day post‐sepsis may lead to an extraneuronal accumulation of the previously released NE in the heart. (This work was supported by NHLBI # 66016).