Background: Parkinson's disease is a degenerative nerve disease due to damage in dopamine-producing neurons in the brain, particularly in the substantia nigra pars compacta.Objective: Identify reduction of alpha synuclein expression on substantia nigra in Parkinson's rat model after given Saccharomyces cerevisae.Patients and methods / Material and methods: This research applied true experimental design by in vivo with draft randomized post test only controlled group. The sample was divided into five groups, each of them consisted of 5 rats, namely, negative control group, positive control group, Treatment Group 1, 2 and 3 (Rotenone + Saccharomyces cerevisae 18 mg/kgBB), 36 mg/kgBW, 72 mg/kgBW which is given for 30 days). Variable measured is alpha synuclein expression.Results: Significant difference in the number of expressions of alpha synuclein between positive control group and negative control group (p = 0000) and treatment group (p = 0.000; 0.000; 0.000); the addition of Saccharomyces cerevisae in Treatment 1, 2 and 3 (18mg/kgBW, 36mg/kgBW, 72mg/kgBW) caused a significant difference compared with positive control group (p = 0.000; 0.000; 0.000); the addition of Saccharomyces cerevisae in Treatment 1 (18 mg/kgBW) caused significant difference in the amount of alpha synuclein expression compared to the Treatment 2 (36mg/kgBW) (p = 0.981), but it showed a significant difference in Treatment 3 (72mg/kgBW) (p = 0000).Conclusion: Addition of Saccharomyces cerevisae decreases alpha synuclein expression in the substantia nigra of Parkinson’s rat models significantly with maximum results at the dose of 72 mg/kgBW. Background: Parkinson's disease is a degenerative nerve disease due to damage in dopamine-producing neurons in the brain, particularly in the substantia nigra pars compacta. Objective: Identify reduction of alpha synuclein expression on substantia nigra in Parkinson's rat model after given Saccharomyces cerevisae. Patients and methods / Material and methods: This research applied true experimental design by in vivo with draft randomized post test only controlled group. The sample was divided into five groups, each of them consisted of 5 rats, namely, negative control group, positive control group, Treatment Group 1, 2 and 3 (Rotenone + Saccharomyces cerevisae 18 mg/kgBB), 36 mg/kgBW, 72 mg/kgBW which is given for 30 days). Variable measured is alpha synuclein expression. Results: Significant difference in the number of expressions of alpha synuclein between positive control group and negative control group (p = 0000) and treatment group (p = 0.000; 0.000; 0.000); the addition of Saccharomyces cerevisae in Treatment 1, 2 and 3 (18mg/kgBW, 36mg/kgBW, 72mg/kgBW) caused a significant difference compared with positive control group (p = 0.000; 0.000; 0.000); the addition of Saccharomyces cerevisae in Treatment 1 (18 mg/kgBW) caused significant difference in the amount of alpha synuclein expression compared to the Treatment 2 (36mg/kgBW) (p = 0.981), but it showed a significant difference in Treatment 3 (72mg/kgBW) (p = 0000). Conclusion: Addition of Saccharomyces cerevisae decreases alpha synuclein expression in the substantia nigra of Parkinson’s rat models significantly with maximum results at the dose of 72 mg/kgBW.