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Obhjective: This research aims to determine the effectiveness difference of Annona muricata leaf extract dose of 100mg/Kg BW (Bodi Weight) and the combination of cefadroxil 45mg/ kg BW and the annona muricata leaf extract 100mg/Kg BW on the 4th day and the 7th day to wards TNF-α level to Sprague Dawley Rat induced with S. aureus. Methods: This research was divided into four treatment groups which contain of five rats induced by S. Aureus 0,2 mlx108CFU, 1x24 hours, group I (negative control) which is only induced by Na. CMC 0,5%, group II (positive control) with Cefadroxil Antibiotics 9 mg, group III with annona muricata leaf extract 100mg/KgBW, and group IV with combination Cefadroxil Antibiotics and annona muricata leaf extract 100 mg/KgBW, every group got treatment twice in a day for five days. TNF-α grade was measured on 4th day and 7th day after the induction of S. aureus than tested by ELISA technique and analyzed by One Way Anova test and Independent sample T-Test. Result: On the 4th day is found the value of p> 0,05 the comparison between the control groups and each group. These indicate that there is no significant difference of the reduction of TNF-α level on the 4th day. On 7th day In the control group and the treatment control of combination of Antibiotics and Annona muricata Leaf Extract, it is found significant difference hith the p value of > 0,05 on the 7th day with average difference 43,26 ng/ml. Conclusion: Combination of Annona muricata leaf extract and Cefadroxil effective against TNF-α levels in Mammae female rat Sprague Dawley-induced Staphylococcus aureus on the 7th day