Previous studies showed andrographolide possesses a strong anti-inflammatory activity.In the present study, we investigated whether andrographolide could restore vascular reactivity in endotoxaemic rats in vivo and explored its mechanisms.After challenged by lipopolysaccharide (LPS, 4 mg/kg, i.p), the rats were treated with andrographolide (1 mg/kg, i.p., 1 mL).The response to norepinephrine of aortic rings with or without perivascular adipose tissue (PVAT) was recorded.The anti-contractile function of PVAT was determined by bioassay experiments.Inducible nitric oxide synthase (iNOS) protein in aortic PVAT was tested by western-blot and immunofluorescence.LPS injection lowered the contraction force induced by norepinephrine in aortic rings with or without PVAT.Andrographolide treatment was able to restore vascular reactivity to norepinephrine.In bioassay experiments, transferring bathing solution incubated with a PVAT+ ring (donor) to a PVAT-ring (recipient) induced relaxation in the recipient in rats treated with vehicles or LPS.However, the relaxing rate of aortic rings from endotoxaemic rats was significantly higher than the rate from rats treated with vehicles.Andrographolide treatment decreased the relaxing effect of PVAT in endotoxaemic rats.The levels of iNOS protein in PVAT were significantly higher in endotoxaemic rats than the rats treated with vehicles determined by western-blot and immunofluorescence.Andrographolide treatment could decrease iNOS protein levels of PVAT in rats treated with LPS.Our results suggest andrographolide protects against LPS-induced vascular hyporeactivity possibly by downregulation of iNOS protein in PVAT.