This study aims to investigate the chemical constituents and anti-inflammatory activity of Talaromyces sp. W21 from the Huixian wetland in Guilin.A new α-pyrone derivative,namely cytospone K (1),together with nine known compounds,namely (3S,4R,5R)-4-hydroxymethyl-3,5-dimethyldihydro-2-furanone (2),lasdiplactone (3),leptosphaerone C (4),annularin A (5),annularin K (6),cladobotrin V (7),2- (2′S-hydroxypropyl) -5-methyl-7-hydroxychromone (8),bacillisporin A (9) and bacillisporin B (10) were isolated and purified from cultures of Talaromyces sp. W21 by using various column chromatography.Their structures were identified by modern spectroscopic techniques and physicochemical properties.Compound 1 was a new α-pyranone derivative,and compounds 2-8 were isolated from the Talaromyces sp. for the first time.The anti-inflammatory activity assay showed that compounds 9 and 10 have a moderate inhibition of NO production induced by LPS in RAW 264.7 cells,with IC₅₀ values of 38.90 ± 0.79 and 35.02 ± 1.03 μmol/L respectively.