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Abstract Objective: This study aimed to analyse the Potential effectiveness effect Annona muricata L. extract as complementary therapy of interleukin-6 (IL-6) level of Sprague-Dawley rats induced by S. aureus. Method: It was a laboratory experiment, with a post-test only control group design. The group was divided into four treatment groups consisting of five rats induced by S. aureus 2 x 107 CFU/ ml, 1 x 24 hours; negative control (1st group) were only given CMC-Na 0.5 %, Positive Control (2nd group) given cefadroxil 45 mg/kg BW, 3rd group given Annona muricata L. extract 100 mg/kg BW, and 4th group given Annona muricata L. extract combined with cefadroxil. Each group was given treatment twice a day (12 hours) for five days. IL-6 levels were measured on the 3rd day (after induction S. aureus or before intervention) and 6th day (after intervention), tested by ELISA technique and data analysed by One Way Anova test and Paired Samples T-test. Results: Giving Annona muricata L. extract only or combined with cefadroxil could reduce levels of IL-6 significantly, when compared with cefadroxil, giving cefadroxil only did not have a significant effect even a decrease in IL-6 is very low, this is different if a combination of Annona muricata L. and cefadroxil. Conclusion: Ethanol extract of Annona muricata L. has the potential as a complementary therapy for mastitis caused by the bacterium S. aureus.