Background and aim: The benefits of manila sapodilla fruit have been widely known empirically in the community, namely raw fruit used for the treatment of typhoid fever. This study is to prove the effect of Manila fruit in reducing levels of tumor necrosis factor alpha (TNF-α). Materials and methods: The design of this study uses a randomized design with Matching Pre test - Post test Comparison Group Design. The animals were divided into negative control group (induced by S. thypi without therapy), and groups treated with 510, and 750 mg/ kg BB of Manila sapodilla (Achras Zapota L) extract, and positive control group treated with Levofloxacin 98 mg / kg BB. Serum TNF-α level was assayed in 4, 10 and 30 days after treatment. Results: A significant decrease in TNF-α concentration was found (p<0.05) in all experimental groups at observation day 4, 10 until the 30th day after treatment. Conclusion: Treatment with Manila sapodilla fruit extract (510 and 750 mg / KgBB) can reduce levels of soluble in TNF-α in Salmonella typhi infected animals.