"It's up to the people," Stedman Graham was quoted as telling The Los Angeles Times. "She would absolutely do it."
"She launched a rocket tonight. I want her to run for president," Meryl Streep told The Washington Post. "I don't think she had any intention (of declaring). But now she doesn't have a choice."
CNN quoted two anonymous "close friends" as saying Winfrey was "actively thinking" about a presidential run although stressing that she had not made up her mind.
If the speculation is wishful thinking, Winfrey's fame and wealth, extraordinary personal story overcoming poverty, teenage rape and pregnancy to build a $2.6 billion fortune and Oscar-nominated acting career, would stack up nicely in her favor.
"I slept on it and came to the conclusion that the Oprah thing isn't that crazy," tweeted Dan Pfeiffer, a former senior advisor to Barack Obama, the president whom Winfrey was credited with helping to elect in 2008.
A March 2017 poll by Quinnipiac University that handed Trump a 41 percent job approval rating, said 52 percent of respondents had a favorable opinion of Winfrey.
In an interview with Bloomberg TV that same month, she hinted that Trump's lack of government experience, had recalibrated her own thoughts. "I thought, 'Oh gee, I don't have the experience, I don't know enough.' And now I'm thinking, 'Oh.'"
'Would she want to?'
Three months later, Winfrey tweeted to her 41 million followers a link to a New York Post editorial that trumpeted her as the Democrats' best hope of beating Trump in 2020.
"You need a star - a grand, outsized, fearless star whom Trump can neither intimidate nor outshine," ran the editorial. "She can do it - in theory. The question is: Would she want to?"
"Thanks for your VOTE of confidence!" responded Winfrey on Twitter.
Raised in Nashville, Milwaukee and Mississippi, she was raped as a 14-year-old by an uncle and became pregnant, until she miscarried the baby.
After college, she went into journalism before reigning for 25 years as queen of the US talk show, ushering in an era of confessional television before becoming the first black woman to own a television network.
At the start of the Golden Globes on Sunday, host Seth Meyers playfully encouraged Winfrey to run against Trump. Becoming the first black woman to accept the Cecil B. De Mille lifetime achievement award, her speech wove together gender, poverty and race.
"For too long, women have not been heard or believed if they dare speak the truth to the power of those men," she said to a standing ovation. "So I want all the girls watching here now to know that a new day is on the horizon."
Would the electorate be ready to put not just another television star but another political outsider in the White House?
"There's a feeling among many in the country that prior political experience is actually a deficit," said Cindy Rosenthal, political science professor at the University of Oklahoma.
But if politics is a money person's game, then the odds are still out.
"There is money around for Oprah, Michelle Obama and George Clooney - but the odds suggest The Donald is going to be hard to beat," said Rupert Adams, spokesman for global betting chain William Hill.