Underserved minority groups are disproportionately absent from the pursuit of careers in science, technology, engineering, and mathematics (STEM) fields. One such underserved population, Native Americans, are particularly underrepresented in STEM fields. Although recent advocacy and outreach designed toward increasing minority involvement in health carerelated occupations have been mostly successful, little is known about the efficacy of outreach programs in increasing minority enthusiasm toward careers in traditional scientific professions. Furthermore, very little is known about outreach among Native American schools toward increasing involvement in STEM. We collaborated with tribal middle and high schools in South Dakota and Nebraska through a National Institutes of Health Science Education Partnership Award to hold a day-long physiology, activity-based event to increase both understanding of physiology and enthusiasm to scientific careers. We recruited volunteer biomedical scientists and trainees from the University of Nebraska Medical Center, Nebraska Wesleyan University, and University of South Dakota. To evaluate the effectiveness of the day of activities, 224 of the ~275-300 participating students completed both a pre- and postevent evaluation assessment. We observed increases in both students self-perceived knowledge of physiology and enthusiasm toward scientific career opportunities after the day of outreach activities. We conclude that activity-based learning opportunities in underserved populations are effective in increasing both knowledge of science and interest in scientific careers.