Pompeo posted the gif to his Twitter page just as Pelosi was lambasting Trump and Republican Senate Majority Leader Mitch McConnell for what she described as "standing in the way" of Democratic policy reform.
Simpsons showrunner Bill Oakley retweeted a response to Pompeo's gif from another user with the caption "Denigrating Simpsons fans didn't work well for the incumbents back in 1992, you smarmy little bastard," a reference to then-President George H.W. Bush saying America's families should be "a little bit more like the Waltons and a little bit less like the Simpsons."
Bush, who was lauding a Depression-era family depicted in a 1970's TV show, went on to lose his reelection bid, ceding the White House to Democrat Bill Clinton.
It wasn't the first time Pompeo had used Lisa Simpson to mock Pelosi.
After the State of the Union speech in February, the secretary of state posted the same clip, earning the wrath of actress Yeardley Smith, who provides the animated character's voice.