Objective: To investigate effect of fluid resuscitation on glycocalyx of rabbits with early septic shock. Methods: Twenty-four rabbits were randomly divided into control group, sepsis group (LPS group), sepsis +10 ml treatment group (10 ml group), and sepsis +30 ml treatment group (30 ml group). Effects of norepinephrine combining with resuscitation fluid on atrial natriuretic peptide (ANP) and plasma syndecan-1 were investigated. Results: ANP level was the lowest in control group, followed by LPS group, 10 ml group and 30 ml group. Plasma syndecan-1 concentration was the lowest in control group, followed by 10 ml group, 30 ml group and LPS group. The expression of syndencan-1 in renal tissues was decreased in the order of control group, 10 ml group, 30 ml group and LPS group. The expression of syndecan-1 and angiotensin-1 in renal tissues was decreased in the order of control group, 10 ml, 30 ml and LPS group. The expression of angiotensin-2, matrix metalloproteinase-2, 7 and intercellular adhesion molecule-1 was increased in 10 ml group, followed by 30 ml group and LPS group. Univariate analysis demonstrated significant differences in ANP among the four groups (all p<0.05), and between-group differences were found (all P<0.05). Conclusion: Vascular endothelial glycocalyx was shedding in rabbits with septic shock. Timely resuscitation with crystalloids in combination with norepinephrine exerts a protective effect on endothelial cell and glycocalyx. An adequate dose of fluid is recommended, as opposed to excessive fluid that is detrimental. Excessive infusion of fluid aggravated glycocalyx damage, further increasing tissue permeability and leading to poor prognosis.