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Background: There is rapidly emerging interest in music interventions in healthcare. Music interventions are widely applicable, inexpensive, without side effects, and easy to use. It is not precisely known how they exert positive effects on health outcomes. Experimental studies in animal models might reveal more about the pathophysiological mechanisms of music interventions. Methods: We performed a systematic review of experimental research in rodents. The electronic databases EMBASE, Medline(ovidSP), Web-Of-Science, PsycINFO, Cinahl, PubMed publisher, Cochrane, and Google scholar were searched for publications between January 1st 1960 and April 22nd 2017. Eligible were English-written, full-text publications on experimental research in rodents comparing music vs. a control situation. Outcomes were categorized in four domains: brain structure and neuro-chemistry; behavior; immunology; and physiology. Additionally, an overview was generated representing the effects of various types of music on outcomes. Bias in studies was assessed with the SYRCLE Risk of Bias tool. A meta-analysis was not feasible due to heterogeneous outcomes and lack of original outcome data. Results: Forty-two studies were included. Music-exposed rodents showed statistically significant increases in neuro-chemistry, such as higher BDNF levels, as well as an enhanced propensity for neurogenesis and neuroplasticity. Furthermore, music exposure was linked with statistically significantly improved spatial and auditory learning, reduced anxiety-related behavior, and increased immune responses. Various statistically significant changes occurred in physiological parameters such as blood pressure and (para)sympathetic nerve activity following music interventions. The majority of studies investigated classical music interventions, but other types of music exerted positive effects on outcomes as well. The SYRCLE risk of bias assessment revealed unclear risk of bias in all studies. Conclusions: Music interventions seem to improve brain structure and neuro-chemistry; behavior; immunology; and physiology in rodents. Further research is necessary to explore and optimize the effect of music interventions, and to evaluate its effects in humans.