The impact of the extraction method on the physiochemicalcharacteristicsand anti-inflammatory effect of polysaccharides from vinegar-baked Radix Bupleuri (VBCPs) was studied. Five extraction methodswere employed to obtain the VBCPs: hot water extraction (HW), ultrasound-assistedextraction (UA), enzyme-assisted extraction (EA), citric acid-assistedextraction (CA), and ammonia-assisted extraction (KA). The resultsshowed that the extraction method affects the yield, characteristics,and anti-inflammatory effect of the polysaccharides significantly.KA produced the highest yield, Ara content, and the strongest effectof enhancing IL-10 secretion. VBCP-EA exhibited the largest molecularweight (Mw), the highest Man content, and the poorest effect on inhibitingNO, VBCP-UA possessed more Gal than other VBCPs, the lowest Mw, anda comparable effect on inhibiting NO and TNF-& alpha; with VBCP-KAand VBCP-CA. All VBCP self-assembled into nanoparticles in solutions,and VBCP-KA presented the lowest particle size. The structure-activityanalysis showed that Mw and Man content are negatively correlatedand Ara content is positively correlated with the NO inhibition andIL-10 secretion effects; Rha and Gal A content are positively correlatedand Glu is negatively correlated with the TNF-& alpha; inhibiting effect.The above results indicated that KA is an efficient method for obtaininganti-inflammatory VBCP, which provides new insight into the extractionof VBCP.