To observe the anti-tumor effects of triptonide on acute monocytic leukemia(AML) in mice and explore its mechanism based on anti-inflammatory activity and modulation of gut microbiota.Methods:Twenty female BALB/c nude mice were subcutaneously injected with AML cell line(U937) to establish a leukemia model.Mice were randomly divided into two groups based on tumor volume，with 8 mice per group.The triptonide group was administered by gavage at a dose of 10 mg/kg，while the control group received an equal volume of physiological saline once daily.After 2 weeks of treatment，mice were euthanized，and samples were collected.Hematoxylin-eosin(HE) staining was used to observe tumor necrosis; immunohistochemistry(IHC) was used to detect protein expression of p-IκB，p-IKK，and p-NF-κB in tumor tissues; enzyme-linked immunosorbent assay(ELISA) was used to measure serum inflammatory mediator levels; 16S rRNA sequencing was used to analyze changes in gut microbiota.Results:Compared with the control group，the triptonide group showed slower tumor growth with a tumor inhibition rate of 43.5%.Tumor tissues in the triptonide group exhibited more necrosis.Serum levels of inflammatory mediators TNF-α，IL-1β，and CRP were significantly reduced(P<0.05).Expression levels of p-IκB，p-IKK，and p-NF-κB in tumor tissues were significantly decreased(P<0.05).Gut microbiota alpha diversity index significantly increased(P<0.01)，and beta diversity showed substantial differences in microbiota composition between the two groups.At the phylum level，the abundance of p__Tenericutes was significantly increased(P<0.05)，while p__Bacteroidetes and p__Firmicutes abundance increased，and p__Proteobacteria abundance decreased.At the genus level，triptonide upregulated beneficial bacteria such as g__Lachnospiraceae_NK4A136_group，g__Alloprevotella，and g__Ruminiclostridium_9，and downregulated pathogenic bacteria such as g__Alistipes，g__Enterorhabdus，and Ruminiclostridium_6.Conclusion:Triptonide exhibits anti-AML effects，and its mechanism may be related to its anti-inflammatory activity and improvement of gut microbiota structure.