It makes a big difference in your life when you stay positive.

The line distills a common theme in DeGeneres’s public persona—optimism as a practical life strategy rather than mere cheerfulness. “Stay positive” implies an ongoing discipline: choosing hopeful interpretations, focusing on workable next steps, and not letting setbacks define one’s identity or future. The “big difference” suggests cumulative effects: attitude shapes behavior (persistence, kindness, risk-taking), which in turn influences relationships and opportunities. Read this way, the quote functions as motivational counsel, emphasizing agency in how one meets adversity, even when one cannot control circumstances.