Objective To investigate the chemical constituents and anti-inflammatory activities of petroleumether and ethyl acetate extracts of Myristica fragrans Houtt. Methods The compounds were separated and purified by using forward and reverse phase silica gel chromatography, preparative thin layer chromatography, sephadex LH-20 and semi-preparative liquid chromatography. The structures of the compounds were identified by comparing the 1H and 13C NMR data with those reported in the literatures. The inhibitory activities of the compounds against LPS-induced NO production in RAW264.7 cells were determined by the Griess assay. Results Fifteen compounds were isolated from the petroleum ether and ethyl acetate extracts of Myristica fragrans. and identified as 2-(4-allyl-2, 6-dimethoxypheNO_xy)-1-(4-hydroxy-3-methoxyphe-nyl) propane (1), iso-lignan (2), 4-(2-(4-allyl-2, 6-dimethoxypheNO_xy)-1-hydroxypropyl)-2, 6-dimethoxyphenol (3), (E)-4-(1-hydroxy-2-(2-methoxy-4-(propenyl) pheNO_xy) propyl)-2-methoxyphenol (4), (-)-miliusfragrin (5), dehydro-diisoeugenol (6), trans-2, 3-dihydro-7-methoxy-2-(3,4-dimethoxy-phenyl)-3-methyl-5-(1-(E)-propenyl) benzofuran (7), (-)-eusiderin A (8), acetyl oleiferin C (9), psoralen (10), 3-(4-hydroxy-3-methoxyphenyl)propane-1, 2-diol (11), 1-(3, 4-dime-thoxyphenyl)propan-2-one (12), broussochalcone B (13), bavachinin (14), malabaricone C (15). The in vitro anti-inflammatory activity assay showed that compounds 13 and 15 strongly inhibited LPS-induced NO release in RAW 264.7 cells with IC50 values of 8.57 ± 0.11 and 12.01 ±v1.27 μmol·L-1, respectively. Compounds 1 and 7 showed moderate inhibitory activities with IC50 of 34.48 ± 3.05 and 42.76 ± 1.53 μmol·L-1, respectively. Conclusion Compounds 5 and 8～14 were isolated from Myristica fragrans for the first time. The in vitro anti-inflammatory activity assay showed that compounds 13 and 15 strongly inhibited LPS-induced NO release in RAW 264.7 cells, compounds 1 and 7 showed moderate inhibitory activities, compounds 2～6, 8～12, and 14 have no activity.