A cheating scandal at Bart and Lisa Simpson's school leads Kent Brockman, the newsreader character in the long-running cartoon, to describe it as "more corrupt than the Italian parliament."
He shows the principal of the school, Seymour Skinner, undercover footage of students cheating at their exams.
"If these children are our future then I for one do not want to live," the news anchor says in the episode, which was broadcast in the United States this week.
The episode sparked a debate among Italians on social media, with some seeing the funny side but others expressing disgust that the venality of politicians had led to Italy being held up as a synonym for corruption.
"We've really hit rock bottom," said one Twitter user.
"It's official – we are now the laughing stock of even the Simpsons," tweeted another.
"If even the Simpsons are taking the mickey, isn't it time to start asking ourselves a few questions?" wrote an Italian woman.
Others were more defiant, saying the United States had more than enough graft of its own.
"This comes from the country that has the largest number of banking scandals in the world," said one Twitter user.
Italy was ranked 72 out of 174 states and territories in Transparency International's most recent Corruption Perceptions Index, which lists countries based on how corrupt their public sector is perceived to be.
The least corrupt countries, jointly at number one, were Finland, New Zealand and Denmark, while the most graft-ridden was Somalia.
Silvio Berlusconi, the three-times prime minister, has faced a wide range of corruption allegations during his 20 years in politics, from tax fraud on a massive scale to abusing his office by having an under age prostitute released from police custody and bribing a Left-wing senator three million euros to join his centre-Right party.